American Journal of Obstetrics & Gynecology

2013-05-01

Information for readers

2013-05-01

New tools for an old quest

Carl P. Weiner — 2013-01-02

Due in great part to the more than 20 years of groundbreaking work by Lo et al, the long-awaited noninvasive prenatal diagnosis of trisomy 21 is almost at hand, perhaps lacking only a few technical enhancements to reduce or eliminate a small false error rate to be widely applicable. Even more exciting is the potential to examine the whole fetal genome in search of disorders not caused by aneuploidy.

Patients, providers, and politicians: we all bear the weight of the obesity epidemic

Paola A. Gehrig — 2013-02-14

To say that there is an obesity epidemic is an understatement. The conditions of overweight (body mass index [BMI], 25-29.9 kg/m2) and obesity (BMI, >30 kg/m2) are becoming the norm in the United States and other countries. In the United States, almost 30% of adult women are overweight, and 36% are obese. These data are comparable with the proportion of women who are overweight in Canada (30%) and England (32%). Increased rates of all-cause mortality, increased rates of cancer incidence, and increased risks of death from cancer have all been attributed to increasing BMI. There are many challenges to addressing the issue of obesity and the role that it plays in women's health. By highlighting the article by Jernigan et al published in this issue, we can begin to address some of the physician practices and attitudes that are related to obesity management in gynecologic oncology in an attempt to further this discussion with our patients and our colleagues, and ultimately to move toward a more comprehensive policy on this issue.

A systematic review of randomized trials assessing human papillomavirus testing in cervical cancer screening

2012-11-19

Our objective was to assess the sensitivity and specificity of human papillomavirus (HPV) testing for cervical cancer screening in randomized trials. We conducted a systematic literature search of the following databases: MEDLINE, CINAHL, EMBASE, and Cochrane. Eligible studies were randomized trials comparing HPV-based to cytology-based screening strategies, with disease status determined by colposcopy/biopsy for participants with positive results. Disease rates (cervical intraepithelial neoplasia [CIN]2 or greater and CIN3 or greater), sensitivity, and positive predictive value were abstracted or calculated from the articles. Six studies met inclusion criteria. Relative sensitivities for detecting CIN3 or greater of HPV testing-based strategies vs cytology ranged from 0.8 to 2.1. The main limitation of our study was that testing methodologies and screening/management protocols were highly variable across studies. Screening strategies in which a single initial HPV-positive test led to colposcopy were more sensitive than cytology but resulted in higher colposcopy rates. These results have implications for cotesting with HPV and cytology as recommended in the United States.

Prenatal treatment of congenital adrenal hyperplasia: risks outweigh benefits

Walter L. Miller, Selma Feldman Witchel — 2012-11-02

Prenatal treatment of congenital adrenal hyperplasia by administering dexamethasone to a woman presumed to be carrying an at-risk fetus has been described as safe and effective in several reports. A review of data from animal experimentation and human trials indicates that first-trimester dexamethasone decreases birthweight; affects renal, pancreatic beta cell, and brain development; increases anxiety; and predisposes to adult hypertension and hyperglycemia. In human studies, first-trimester dexamethasone is associated with orofacial clefts, decreased birthweight, poorer verbal working memory, and poorer self-perception of scholastic and social competence. Numerous medical societies have cautioned that prenatal treatment of congenital adrenal hyperplasia with dexamethasone should only be done in prospective clinical research settings with institutional review board approval, and therefore is not appropriate for routine community practice.

Phenotyping clinical disorders: lessons learned from pelvic organ prolapse

2012-11-29

Genetic epidemiology, the study of genetic contributions to risk for disease, is an innovative area in medicine. Although research in this arena has advanced in other disciplines, few genetic epidemiological studies have been conducted in obstetrics and gynecology. It is crucial that we study the genetic susceptibility for issues in women's health because this information will shape the new frontier of personalized medicine. To date, preterm birth may be one of the best examples of genetic susceptibility in obstetrics and gynecology, but many areas are being evaluated including endometriosis, fibroids, polycystic ovarian syndrome, and pelvic floor disorders. An essential component to genetic epidemiological studies is to characterize, or phenotype, the disorder to identify genetic effects. Given the growing importance of genomics and genetic epidemiology, we discuss the importance of accurate phenotyping of clinical disorders and highlight critical considerations and opportunities in phenotyping, using pelvic organ prolapse as a clinical example.

Staged endovascular and surgical treatment of slow-flow vulvar venous malformations

Naiem Nassiri, Teresa M.J. O, Robert J. Rosen, Jacques Moritz, Milton Waner — 2013-02-08

Objective: The objective of the study was to report our experience in a rare series of treated symptomatic slow-flow vulvar venous malformations (VVMs) using a staged, multidisciplinary approach. Study Design: Consecutive patients with symptomatic lesions treated over a 7 year period (2005-2012) were followed up for technical success, resolution of symptoms, aesthetic outcomes, and complications. Direct endovenous sclerotherapy (DEVS) using sodium tetradecyl sulfate (STS) foam was performed in all patients under ultrasound and contrast-enhanced fluoroscopic guidance. Surgical excision and layered primary closure was performed within 24 hours after the last DEVS session. Results: Eleven patients (mean age, 25 years; range, 4–43 years) were treated. Presenting symptoms included pain (n = 11), soft tissue swelling (n = 11), local heaviness (n = 11), dyspareunia (n = 2), and dysmenorrhea (n = 2). Most were isolated lesions (n = 8). There were 2 cases of Klippel-Trénaunay syndrome and 1 case of Maffucci syndrome. The latter required Nd:YAG laser photocoagulation prior to sclerotherapy. On average, approximately 3 DEVS sessions were required prior to surgical excision (range, 1–6). Mean estimated surgical blood loss was 130 mL (range, 20–400 mL). Mean follow-up was 23 months (range, 3–55 months). Elimination of pain and soft tissue redundancy was achieved in all patients with satisfactory aesthetic outcomes. All patients experienced minor pain and swelling after DEVS. Following surgical excision, there was 1 case of hematoma and wound dehiscence requiring surgical evacuation. No other reinterventions, endovascular or surgical, were required. Conclusion: VVMs require increased awareness and appropriate preoperative evaluation for proper identification and treatment. A multidisciplinary approach can provide improvement in clinical signs and symptoms with satisfactory cosmesis and minimal complications.

A randomized trial comparing conventional and robotically assisted total laparoscopic hysterectomy

2013-02-11

Objective: The purpose of this study was to compare operative time and intra- and postoperative complications between total laparoscopic hysterectomy and robotic-assisted total laparoscopic hysterectomy. Study Design: This study was a blinded, prospective randomized controlled trial conducted at 2 institutions. Subjects consisted of women who planned laparoscopic hysterectomy for benign indications. Preoperative randomization to total laparoscopic hysterectomy or robotic-assisted total laparoscopic hysterectomy was stratified by surgeon and uterine size (> or ≤12 weeks). Validated questionnaires, activity assessment scales, and visual analogue scales were administered at baseline and during follow-up evaluation. Results: Sixty-two women gave consent and were enrolled and randomly assigned; 53 women underwent surgery (laparoscopic, 27 women; robot-assisted, 26 women). There were no demographic differences between groups. Compared with laparoscopic hysterectomy, total case time (skin incision to skin closure) was significantly longer in the robot-assisted group (mean difference, +77 minutes; 95% confidence interval, 33–121; P < .001] as was total operating room time (entry into operating room to exit; mean difference, +72 minutes; 95% confidence interval, 14–130; P = .016). Mean docking time was 6 ± 4 minutes. There were no significant differences between groups in estimated blood loss, pre- and postoperative hematocrit change, and length of stay. There were very few complications, with no difference in individual complication types or total complications between groups. Postoperative pain and return to daily activities were no different between groups. Conclusion: Although laparoscopic and robotic-assisted hysterectomies are safe approaches to hysterectomy, robotic-assisted hysterectomy requires a significantly longer operative time.

Metabolomic analysis for first-trimester Down syndrome prediction

2013-01-10

Objective: The objective of the study was to perform first-trimester maternal serum metabolomic analysis and compare the results in aneuploid vs Down syndrome (DS) pregnancies. Study Design: This was a case-control study of pregnancies between 11+0 and 13+6 weeks. There were 30 DS cases and 60 controls in which first-trimester maternal serum was analyzed. Nuclear magnetic resonance-based metabolomic analysis was performed for DS prediction. Results: Concentrations of 11 metabolites were significantly different in the serum of DS pregnancies. The combination of 3-hydroxyisovalerate, 3-hydroxybuterate, and maternal age had a 51.9% sensitivity at 1.9% false-positive rate for DS detection. One multimarker algorithm had 70% sensitivity at 1.7% false-positive rate. Novel markers such as 3-hydroxybutyrate, involved in brain growth and myelination, and 2-hydroxybutyrate, involved in the defense against oxidative stress, were found to be abnormal. Conclusion: The study reports novel metabolomic markers for the first-trimester prediction of fetal DS. Metabolomics provided insights into the cellular dysfunction in DS.

Recurrence of small-for-gestational-age pregnancy: analysis of first and subsequent singleton pregnancies in The Netherlands

2013-02-18

Objective: Small-for-gestational-age (SGA) neonates are at increased risk of adverse pregnancy outcome. Our objective was to study the recurrence rate of SGA in subsequent pregnancies. Study Design: A prospective national cohort study of all women with a structurally normal first and subsequent singleton pregnancy from 1999-2007. SGA was defined as birthweight <5th percentile for gestation. We compared the incidence and recurrence rate of SGA for women in total and with and without a hypertensive disorder (HTD) in their first pregnancy. Moreover, we assessed the association between gestational age at first delivery and SGA recurrence. Results: We studied 259,481 pregnant women, of whom 12,943 women (5.0%) had an SGA neonate in their first pregnancy. The risk of SGA in the second pregnancy was higher in women with a previous SGA neonate than for women without a previous SGA neonate (23% vs 3.4%; adjusted odds ratio, 8.1; 95% confidence interval, 7.8−8.5) and present in both women with and without an HTD in pregnancy. In women without an HTD, the increased recurrence risk was independent of the gestational age at delivery in the index pregnancy; whereas in women with an HTD, this recurrence risk was increased only when the woman with the index delivery delivered at >32 weeks' gestation. Conclusion: Women with SGA in their first pregnancy have a strongly increased risk of SGA in the subsequent pregnancy and first pregnancy SGA delivers a significant contribution to the total number of second pregnancy SGA cases.

Risk of stillbirth after 37 weeks in pregnancies complicated by small-for-gestational-age fetuses

2013-03-25

Objective: The evidence for delivering small-for-gestational-age (SGA) fetuses at 37 weeks remains conflicting. We examined the risk of stillbirth per week of gestation beyond 37 weeks for pregnancies complicated by SGA. Study Design: Singleton pregnancies undergoing routine second trimester ultrasound from 1990-2009 were examined retrospectively. The risk of stillbirth per 10,000 ongoing SGA pregnancies with 95% confidence intervals (CIs) was calculated for each week of gestation ≥37 weeks. Using a life-table analysis with correction for censoring, conditional risks of stillbirth, cumulative risks of stillbirth per 10,000 ongoing SGA pregnancies and relative risks (RRs) were calculated with 95% CIs for each week of gestation. Results: Among 57,195 pregnancies meeting inclusion criteria the background risk of stillbirth was 56/10,000 (95% CI, 42.3−72.7) with stillbirth risk for SGA pregnancies of 251/10,000 (95% CI, 221.2−284.5). The risk of stillbirth after the 37th week was greater compared with pregnancies delivered in the 37th week (47/10,000, 95% CI, 34.6−62.5 vs 21/10,000, 95% CI, 13.0−32.1; RR, 2.2; 95% CI, 1.3−3.7). The cumulative risk of stillbirth rose from 28/10,000 ongoing SGA pregnancies at 37 weeks to 77/10,000 at 39 weeks (RR, 2.75; 95% CI, 1.79−4.2). Among pregnancies complicated by SGA <5% the cumulative risk of stillbirth at 38 weeks was significantly greater than the risk at 37 weeks (RR, 2.3; 95% CI, 1.4−3.8). Conclusion: There is a significantly increased risk of stillbirth in pregnancies complicated by SGA delivered after the 37th week. Given these findings, we advocate a policy of delivery of SGA pregnancies 37-38 weeks.

Maternal seizure disorder and risk of adverse pregnancy outcomes

2013-02-04

Objective: We sought to estimate the association between maternal seizure disorder and adverse pregnancy outcomes. Study Design: We performed a retrospective cohort study of singleton, nonanomalous pregnancies. Women with self-reported seizure disorder were compared to women without medical problems. The primary outcome was intrauterine growth restriction (IUGR) <10th percentile. Secondary outcomes included IUGR <5th percentile, stillbirth, preeclampsia, and preterm delivery. A sensitivity analysis was performed using women who reported using antiepileptics to estimate the impact of disease severity on pregnancy outcomes. Results: Of 47,118 women, 440 reported a seizure disorder. Women with seizure disorder were not at increased risk of IUGR <10th percentile (adjusted odds ratio, 1.11; 95% confidence interval, 0.82–1.50), IUGR <5th percentile, stillbirth, preeclampsia, or preterm delivery. The results were similar in the sensitivity analysis of women taking antiseizure medications. Conclusion: Our results suggest women with a seizure disorder are not at increased risk of IUGR, stillbirth, preeclampsia, or preterm delivery.

Seeking the mechanism(s) of action for corticosteroids in HELLP syndrome: SMASH study

2013-02-04

Introduction: Administration of dexamethasone to the hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome patients (10 mg intravenously [IV] every 12 hours) shortens the disease course and reduces maternal morbidity in patients treated at the University of Mississippi Medical Center (UMMC), associated with this severe form of preeclampsia. However, the pathophysiological mechanisms involved with this intervention remain unclear. Objective: We sought to investigate the potential role of IV dexamethasone to restore the imbalance among antiangiogenic and inflammatory factors known to be significantly elevated in women with HELLP syndrome. Study Design: This was a single-center prospective study of women diagnosed with HELLP syndrome who were treated for IV dexamethasone at UMMC. Blood was drawn prior to dexamethasone administration and again 12 and 24 hours after the initial dexamethasone administration. Enzyme-linked immune assays were used to measure circulating inflammatory cytokines and antiangiogenic factors. A repeated-measures analysis of variance was used to analyze the data collected before, after, and during dexamethasone administration. Results: Seventeen women with HELLP syndrome were enrolled in this study. Dexamethasone significantly decreased evidence of hemolysis (P = .002) and liver enzymes (P = .003), and significantly increased platelets (P = .0001) within 24 hours of administration. Circulating interleukin-6 levels after 24 hours were decreased (P < .001); soluble fms-like tyrosine kinase-1 and soluble endoglin were also significantly decreased by 24 hours after dexamethasone administration (P < .002 and P < .004, respectively). There were no significant differences in circulating levels of placental growth factor (P = .886) due to dexamethasone administration. Angiotensin II receptor autoantibody levels were unchanged by dexamethasone administration. Conclusion: We conclude that 1 important mechanism of dexamethasone administration is to blunt the release of both antiangiogenic and inflammatory factors suggested to play role in the pathophysiology of HELLP syndrome.

Maternal magnesium supplementation reduces intrauterine growth restriction and suppresses inflammation in a rat model

2013-03-11

Objective: Intrauterine growth restriction (IUGR) is associated with increased inflammatory responses. We sought to investigate whether magnesium (Mg) attenuates inflammation and IUGR in a rat model.Study design: Pregnant Wistar rats (12 weeks, gestational day 18) were randomly assigned to 1 of 4 groups: normal diet with bilateral uterine artery ligation (BL) (n = 6) or sham surgery (SH) (n = 5); and Mg chloride (MgCl2) 1% (wt/vol) in the drinking water throughout gestation + BL (MgBL) (n = 6) or SH (MgSH) (n = 5). Dams were euthanized 24 hours postsurgery (gestational day 19). Maternal plasma, fetal plasma (pooled), individual amniotic fluid (AF) samples, and placentas (PL) were collected and assessed from live fetal pups only (BL, n = 36; SH, n = 20; MgBL, n = 20; MgSH, n = 20). All samples were analyzed for cytokines/chemokines (interleukin [IL]-6, IL-1β, chemokine [C-X-C motif] ligand 1 [CXCL1], chemokine [C-C motif] ligand 2 [CCL2], and tumor necrosis factor [TNF-α] sensitivity <3 pg/mL) using a multiplex platform. Data were analyzed using Mann Whitney, analysis of variance, and Fisher exact tests.Results: The incidence of IUGR (pup weight <10th percentile of SH) in the MgBL group was significantly lower (31%) than the BL group (86.3%) (relative risk, 0.36; 95% confidence interval, 0.2–0.6; P < .0001). BL significantly increased AF levels of IL-6, IL-1β, TNF-α (P < .05), and CCL2 (P < .001) vs SH and PL levels of IL-6, IL-1β, CCL2 and CXCL1 (P < .001), and TNF-α (P < .05) vs SH. Maternal MgCl2 supplementation significantly decreased IL-1β, TNF-α, and CCL2 levels in AF and IL-1β in PL tissues of MgBL vs BL rats (P < .0001).Conclusion: Maternal oral MgCl2 supplementation reduced BL-induced IUGR by 64% and suppressed cytokine/chemokine levels in the AF and PL.

First-trimester detection of fetal anomalies in pregestational diabetes using nuchal translucency, ductus venosus Doppler, and maternal glycosylated hemoglobin

2013-01-28

Objective: The frequency of fetal anomalies in women with pregestational diabetes correlates with their glycemic control. This study aimed to assess the predictive performance of first-trimester fetal nuchal translucency (NT), ductus venosus (DV) Doppler, and hemoglobin A1c (HbA1c) to predict fetal anomalies in women with pregestational diabetes. Study Design: This was a prospective observational study of patients undergoing first-trimester NT with DV Doppler. Screening performance was tested for first-trimester parameters to detect fetal anomalies. Results: Of 293 patients, 17 had fetal anomalies (11 cardiac, 7 major, 3 multisystem). All anomalous fetuses were suspected prenatally. One had NT >95th centile, 2 had reversed DV a-wave, and 13 had HbA1c >7.0%. The HbA1c was the primary determinant of anomalies (r2, 0.15; P < .001) and >8.35% was the optimal cutoff for prediction of anomalies with an area under the curve of 0.72 (95% confidence interval, 0.57–0.88). Therefore, first-trimester prediction of anomalies was best in women with increased NT or HbA1c >8.3% (sensitivity 70.6%, specificity 77.4%, positive predictive value 16.2%, negative predictive value 97.7%, P < .001). Conclusion: In women with pregestational diabetes and poor glycemic control, an increased NT increases risks for major fetal anomalies. Second-trimester follow-up is required to achieve accurate prenatal diagnosis.

Long-term alterations in maternal plasma proteome after sFlt1–induced preeclampsia in mice

2013-03-15

Objective: Preeclampsia is associated with long-term adverse maternal health, such as cardiovascular and metabolic diseases. The objective of this study was to determine whether preeclampsia in a well-characterized animal model that was induced by overexpression of soluble fms-like tyrosine kinase-1 (sFlt1) results in alterations in the maternal circulating proteome that persist long after delivery. Study Design: CD-1 mice at day 8 of gestation were injected with adenovirus that carried sFlt1 or the murine immunoglobulin G2α Fc fragment as control. Depleted maternal plasma was analyzed 6 months after delivery by label-free liquid chromatography–mass spectrometry assay. The tandem mass spectrometry data were searched against a mouse database, and the resultant intensity data were used to compare abundance of proteins across disease/control plasma pool. Results were analyzed with ingenuity pathways analysis. Right-tailed Fisher exact test was used to calculate a probability value. Results: Of 150 proteins that are common for both groups, ingenuity pathways analysis determined 105 proteins that were ready for analysis. Diseases and disorders analysis showed significant enrichment of proteins that are associated with cardiovascular disease. Within this cluster, the most abundant proteins were associated with vascular disease, atherosclerosis, and atherosclerotic lesions. Other top disease clusters were inflammatory response, organismal injury and abnormalities, and hematologic and metabolic disease. Conclusion: Exposure to sFlt1-induced preeclampsia alters multiple biologic functions in mothers that persist later in life. Our results suggest that some of the long-term adverse outcomes that are associated with preeclampsia actually may be a consequence rather than a mere unmasking of an underlying predisposition. If similar results are found in humans, the development of preventive strategies for preeclampsia should also improve long-term maternal health.

Maternal plasma 25-hydroxyvitamin D levels, angiogenic factors, and preeclampsia

2013-05-01

Objective: The objective of the study was to examine the associations of maternal plasma levels of 25-hydroxyvitamin D [25(OH)D] with angiogenesis and endothelial dysfunction indicators: soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and risk of preeclampsia. Study Design: In this prospective cohort study (n = 697), maternal plasma 25(OH)D levels were measured at 12-18 and 24-26 weeks; sFlt-1, PlGF, ICAM-1, and VCAM-1 levels were measured at 24-26 weeks. Results: Maternal PlGF levels were significantly lower in women with 25(OH)D less than 50 nmol/L at 12-18 weeks (median, 449.5 vs 507.9 pg/mL, P = 0.04) and 24-26 weeks (median, 450.4 vs 522.5 pg/mL, P = 0.007). Both maternal 25(OH)D and PlGF levels were inversely associated with the risk of preeclampsia (both P < .05). However, based on a test of interaction, there was no evidence that the association between vitamin D and preeclampsia depended on the level of PlGF. Conclusion: Maternal vitamin D deficiency is associated with low PlGF levels and increased preeclampsia risk. However, our data do not support the hypothesis that the association between vitamin D deficiency and preeclampsia is mediated by impaired angiogenesis.

Correction

2013-02-27

January 2013 (vol. 208, no. 1, page 11) Society for Maternal-Fetal Medicine, Simpson LL. Twin-twin transfusion syndrome: SMFM Clinical Guideline. Am J Obstet Gynecol 208;3:3-18.

Significance of growth discordance in appropriately grown twins

2013-01-30

Objective: We sought to determine the perinatal risks associated with growth discordance in appropriately grown twin gestations. Study Design: We conducted a retrospective cohort study of all twin gestations excluding those complicated by monoamnionicity, twin-twin transfusion syndrome, structural anomalies, selective reduction, or a birthweight <10th percentile. Growth discordance was defined as ≥20%. Outcomes considered were stillbirth, preterm delivery <34 weeks and <28 weeks, and admission to the neonatal intensive care unit. Analyses were stratified by chorionicity. Results: Of 895 included dichorionic pregnancies, 63 (7.0%) were discordant. Discordant dichorionic twins were not at increased risk of preterm delivery <34 weeks (34.9% vs 25.6%; relative risk [RR], 1.4; 95% confidence interval [CI], 1.0−1.9), preterm delivery <28 weeks (3.2% vs 2.8%; RR, 1.1; 95% CI, 0.3−4.8), or admission to intensive care (26.9% vs 23.5%; RR, 1.5; 95% CI, 1.0−2.3). We had >90% power to detect a 2.5-fold increase in preterm delivery and admission to the neonatal intensive care unit in dichorionic twins. Of 250 monochorionic pregnancies, 23 (9.2%) were discordant. Monochorionic twin pregnancies were at increased risk of preterm delivery <34 weeks (65.2% vs 26.4%; RR, 2.5; 95% CI, 1.7−3.6), preterm delivery <28 weeks (34.8% vs 4.0%; RR, 8.8; 95% CI, 3.7−20.5), and admission to intensive care (68.2% vs 23.3%; RR, 2.9; 95% CI, 2.0−4.3). Conclusion: In appropriately grown twins, growth discordance is a risk factor for adverse perinatal outcomes in monochorionic, but not dichorionic, twins. Discordant monochorionic twins may benefit from increased antenatal surveillance.

DNA methylation at imprint regulatory regions in preterm birth and infection

2013-03-13

Objective: To aid in understanding long-term health consequences of intrauterine infections in preterm birth, we evaluated DNA methylation at 9 differentially methylated regions that regulate imprinted genes by type of preterm birth (spontaneous preterm labor, preterm premature rupture of membranes, or medically indicated [fetal growth restriction and preeclampsia]) and infection status (chorioamnionitis or funisitis). Study Design: Data on type of preterm birth and infection status were abstracted from medical records and standardized pathology reports in 73 preterm infants enrolled in the Newborn Epigenetics STudy, a prospective cohort study of mother-infant dyads in Durham, NC. Cord blood was collected at birth, and infant DNA methylation levels at the H19, IGF2, MEG3, MEST, SGCE/PEG10, PEG3, NNAT, and PLAGL1 differentially methylated regions were measured using bisulfite pyrosequencing. One-way analyses of variance and logistic regression models were used to compare DNA methylation levels by type of preterm birth and infection status. Results: DNA methylation levels did not differ at any of the regions (P > .20) between infants born via spontaneous preterm labor (average n = 29), preterm premature rupture of membranes (average n = 17), or medically indicated preterm birth (average n = 40). Levels were significantly increased at PLAGL1 in infants with chorioamnionitis (n = 10, 64.4%) compared with infants without chorioamnionitis (n = 63, 57.9%), P < .01. DNA methylation levels were also increased at PLAGL1 for infants with funisitis (n = 7, 63.3%) compared with infants without funisitis (n = 66, 58.3%), P < .05. Conclusion: Dysregulation of PLAGL1 has been associated with abnormal development and cancer. Early-life exposures, including infection/inflammation, may affect epigenetic changes that increase susceptibility to later chronic disease.

Down syndrome maternal serum marker screening after 18 weeks of gestation: a countrywide study

2013-01-28

Objective: The objective of the study was to evaluate the efficacy of maternal serum markers in detecting Down syndrome after 18 weeks of gestation in women who book late for maternity care in a large national retrospective study. Study Design: During the period 2007-2012, 27,648 women, regardless of maternal age (17.4% were 35 years old and over), were included in a late Down syndrome screening program (18+0 to 35+6 weeks) using the maternal serum markers alpha-fetoprotein and human chorionic gonadotrophin-beta. Samples were assayed in a single laboratory. A dataset of median markers previously established in our laboratory was used for risk calculation. The control group consisted of 27,648 women (14+0 to 17+6 weeks) randomly selected from the routine database. Results: When the later screening group was compared with the standard second-trimester control group, the median multiples of medians (1.01 vs 0.98 for alpha-fetoprotein, 1.03 vs 0.98 for human chorionic gonadotrophin-beta), median risks (1 of 2414 vs 1 of 2720), false-positive rates (11.1% vs 11.6%), and trisomy 21 detection rates (83.3% vs 85.7%) did not differ significantly. Conclusion: Late Down syndrome maternal serum screening is feasible with a good sensitivity/specificity compromise throughout gestation and is of clinical value in late-booking women.

Modulation of lipopolysaccharide-induced chorioamnionitis by Ureaplasma parvum in sheep

2013-02-13

Objective: Ureaplasma colonization in the setting of polymicrobial flora is common in women with chorioamnionitis, and is a risk factor for preterm delivery and neonatal morbidity. We hypothesized that Ureaplasma colonization of amniotic fluid would modulate chorioamnionitis induced by Escherichia coli lipopolysaccharide (LPS). Study Design: Sheep received intraamniotic (IA) injections of media (control) or live Ureaplasma either 7 or 70 days before delivery. Another group received IA LPS 2 days before delivery. To test for interactions, U parvum–exposed animals were challenged with IA LPS, and delivered 2 days later. All animals were delivered preterm at 125 ± 1 day of gestation. Results: Both IA Ureaplasma and LPS induced leukocyte infiltration of chorioamnion. LPS greatly increased the expression of proinflammatory cytokines and myeloperoxidase in leukocytes, while Ureaplasma alone caused modest responses. Interestingly, 7-day but not 70-day Ureaplasma exposure significantly down-regulated LPS-induced proinflammatory cytokines and myeloperoxidase expression in the chorioamnion. Conclusion: Acute (7-day) U parvum exposure can suppress LPS-induced chorioamnionitis.

Safe conception for HIV-discordant couples: insemination with processed semen from the HIV-infected partner

2013-02-11

Objective: The objective of the study was to evaluate the safety of semen washing with intrauterine insemination (SW-IUI) for achieving pregnancy when the man is human immunodeficiency virus (HIV) infected and the woman is HIV negative. Study Design: We conducted a retrospective analysis of 635 HIV-discordant couples enrolled in a SW-IUI program and followed up 367 Italian women. We computed pregnancy, live birth, and multiple delivery rates and assessed the women's postinsemination HIV status. Results: The retrospective analysis included 635 couples (2113 SW-IUI cycles): 41% of the women (95% confidence interval [CI], 37–45%) had a live birth (per-cycle live birth rate 13%; 95% CI, 11–14%). HIV status after SW-IUI was negative when available but unknown for 26% of the women: missing HIV status was not associated with correlates of HIV risk. The follow-up study included 367 couples (1365 cycles): 47% of the women (95% CI, 42–52%) had a live birth (per-cycle rate 14%; 95% CI, 12–16%). Ascertainment of postinsemination HIV status was complete and confirmed no HIV transmission attributable to SW-IUI. The upper 95% confidence limit of the HIV transmission rate was 1.8 per 1000 cycles in the retrospective analysis and 2.7 per 1000 cycles in the follow-up study. Conclusion: SW-IUI appears to be a safe and effective method for achieving pregnancy in HIV-discordant couples in which the man is HIV infected.

Seasonal variations of human sperm cells among 6455 semen samples: a plausible explanation of a seasonal birth pattern

Eliahu Levitas, Eitan Lunenfeld, Noemi Weisz, Michael Friger, Iris Har-Vardi — 2013-02-11

Objective: To compare the different sperm parameters according to season of the year on sperm production day and the season 70 days prior (during spermatogenesis). Study Design: Retrospective Andrology Laboratory data comparison. A total of 6455 consecutive semen samples were collected as part of the basic fertility evaluation of 6447 couples. According to sperm concentration, the samples were classified as Normozoospermic or Oligozoospermic and analyzed in relation to the season. Results: The sperm concentration and percentage of fast motility showed a significant decrease from spring toward summer and fall (P < .001) with recovery noticed during the winter. As well, the highest percentage of normal sperm morphology was observed during the winter months. Conclusion: Seasonal sperm pattern seems to be a circannual-rhythmic phenomenon. The winter and spring semen patterns are compatible with increased fecundability and may be a plausible explanation of the peak number of deliveries during the fall.

Correction

2013-02-20

Supplement to January 2013 (vol. 208, no. 1, page S93) The byline in an abstract published in the January 2013 supplement to the Journal representing the program of the 33rd annual meeting of the Society for Maternal-Fetal Medicine omitted the name of the seventh (last) author.

Obesity management in gynecologic cancer survivors: provider practices and attitudes

Amelia M. Jernigan, Ana I. Tergas, Andrew J. Satin, Amanda N. Fader — 2013-02-08

Objective: Obesity is associated with the development and risk of death from several women's cancers. The study objective was to describe and compare oncologic providers' attitudes and practices as they relate to obesity counseling and management in cancer survivors. Study Design: Society of Gynecologic Oncology members (n = 924) were surveyed with the use of a web-based, electronic questionnaire. χ2 and Fisher exact tests were used to analyze responses. Results: Of the 240 respondents (30%), 92.9% were practicing gynecologic oncologists or fellows, and 5.1% were allied health professionals. Median age was 42 years; 50.8% of the respondents were female. Of the respondents, 42.7% reported that they themselves were overweight/obese and that ≥50% of their survivor patients were overweight/obese. Additionaly, 82% of the respondents believed that discussing weight would not harm the doctor-patient relationship. Most of the respondents (95%) agreed that addressing lifestyle modifications with survivors is important. Respondents believed that gynecologic oncologists (85.1%) and primary care providers (84.5%) were responsible for addressing obesity. More providers who were ≤42 years old reported undergoing obesity management training (P < .001) and were more likely to believe that survivors would benefit from obesity education than providers who were >42 years old (P = .017). After initial counseling, 81.5% of the respondents referred survivors to other providers for obesity interventions. Conclusion: Oncology provider respondents believe that addressing obesity with cancer survivors is important. Providers believed themselves to be responsible for initial counseling but believed that obesity interventions should be directed by other specialists. Further research is needed to identify barriers to care for obese cancer survivors and to improve physician engagement with obesity counseling in the “teachable moment” that is provided by a new cancer diagnosis.

A contemporary analysis of epidemiology and management of vaginal intraepithelial neoplasia

2013-02-04

Objective: The purpose of this study was to review a large cohort of patients with vaginal intraepithelial neoplasia (VAIN) and to analyze the epidemiology and outcomes with various treatment modalities. Study Design: A retrospective chart review was performed that encompassed patients who were treated for VAIN at a single center from 1990-2007. Demographics, disease characteristics, referring cytology, and histologic information were recorded. Primary outcome was recurrence or progression to carcinoma. Statistical analyses were performed with statistical software. Results: One hundred sixty-three women were included in the study: median age, 50 years (range, 21–84 years); white, 87%; current or previous smokers, 35%. At the time of diagnosis, 23% of the women had VAIN1; 37% of the women had VAIN2, and 35% of the women had VAIN3. Referral Papanicolaou smear results of high-grade squamous intraepithelial lesion or atypical glandular cells revealed VAIN2 or VAIN3 in 89% of cases (P = .0019) vs 53% of cases with low-grade squamous intraepithelial lesion. The median follow-up period was 18 months (range, 1–194 months). VAIN1 was observed in 70% of cases; 71% of patients who were treated for VAIN1 had recurrence or progression. VAIN2 was treated in 77% of patients; 53% of those who were treated had recurrence or progression. VAIN3 was treated in 94% of cases; 31% of them had recurrence or progression. Risk of recurrence was not correlated to VAIN type (P = .3). Six carcinomas were discovered in patients with VAIN2 and VAIN3. Median time to progression was 17 months for VAIN1, 11 months for VAIN2, and 11 months for VAIN3 (P = .036). Conclusion: Despite the subtype, VAIN often recurs but does so more quickly with higher grade dysplasia.

Clinical analysis of ovarian epithelial carcinoma with coexisting pelvic endometriosis

2012-12-07

Objectives: To explore the differences between women with endometiosis associated ovarian cancer and typical epithelial ovarian cancer. Study Design: The medical charts of total 226 patients with epithelial ovarian cancer treated at Peking Union Medical College Hospital between March 2011 and March 2012 were reviewed. Histology evaluation determined endometiosis associated ovarian cancer (n = 17) or nonendometiosis associated ovarian cancer (n = 209). Results: Compared with nonendometiosis associated ovarian cancer, patients with endometiosis associated ovarian cancer were proved: (1) to be younger and more likely to be premenopausal at diagnosis of epithelial ovarian cancer (P = .03 and .005, respectively); (2) to have lower preoperative serum level of Ca125 (mean: 122.9 vs 1377.5 U/mL, P < .001) and more likely to display normal Ca125 level (P < .001); (3) to be identified at the earlier stage (stage I, P < .001); (4) to have completely different distribution of histological subtypes (significant overrepresentation of clear cell and endometrioid carcinoma). Conclusion: As such, patients with endometiosis associated ovarian cancer differ from nonendometiosis associated ovarian cancer in many of their critical clinical and biologic characteristics.

Ovarian epithelial carcinoma with pelvic endometriosis: Wang et al

2013-03-18

The article below summarizes a roundtable discussion of a study published in this issue of the Journal in light of its methodology, relevance to practice, and implications for future research. Article discussed:Wang S, Qui L, Lang JH, et al. Clinical analysis of ovarian epithelial carcinoma with coexisting pelvic endometriosis. Am J Obstet Gynecol 2013;208:413.e1-5.

The case of the sinister spores: The patient was hospitalized for a menacing infection in the second trimester of pregnancy

Shivani Patel, Richard H. Lee — 2013-02-11

A 30-year-old Filipino woman was at approximately 14 weeks' gestation in her first pregnancy when she presented to her obstetrician with a 1 week history of headaches, nausea, and vomiting. At that time, she was diagnosed with migraine headaches. About 2 weeks later, she visited the emergency department and reported unrelenting headaches, continued nausea and vomiting, joint pain, and fevers. Physical examination uncovered circular erythematous lesions on her right thumb and back. Lumbar puncture and cervical lymph node biopsy were performed.

What is a laborist?

Fouad Atallah — 2013-01-10

We read with great pleasure the article by Olson et al in the August 2012 issue. According to their definition, I am a part-time, full-service hospitalist. My time as a laborist is 5-37% of my weekly hours in the hospital. We share the belief that it is too early to pass a judgment on the effects of the laborist model on efficiency, processes, outcomes, patient and provider satisfaction, and medical education and that further studies are needed. As exposed in the article, this model is the culmination of a change in the professional climate, the practice of the specialty, paralleled by a generational shift.

Is early amniotomy in nulliparous labor induction really efficient?

Taner Kasapoglu — 2013-01-10

Thank you for publishing an article about the concept of early amniotomy in nulliparous labor induction. It is really a special interest topic in the field of obstetrics that most of us considerably encounter in clinical practice every day. I also congratulate all the authors who contributed to this successfully and rationally designed article. However, there seems to be something wrong with the statistical analysis performed in the study.

Reply

George A. Macones — 2013-01-10

We thank Dr Kasapoglu for his interest in our article on the role of early amniotomy in nulliparous labor induction. Dr Kasapoglu raises 2 points in his letter. First, he has some concerns about our sample size as it relates to one of the primary outcomes: proportion of women delivered with 24 hours. I believe that he assumed that this was limited to those women who delivered vaginally. In fact, this primary outcome included women who both delivered vaginally and by cesarean.

Trends in the rate of invasive procedures after the addition of the intrauterine tamponade test to a protocol for management of severe postpartum hemorrhage

Delphine Héquet, Sophie Lubrano, Emmanuel Barranger — 2013-01-10

We read with interest the recent article from Laas et al. This was a really interesting study concerning a new treatment of a main cause of maternal death. We want to congratulate the authors for evaluating the efficiency of the intrauterine tamponade test by Bakri balloon in severe postpartum hemorrhage. Literature about Bakri balloon tamponade is limited to case reports or a few retrospective series. Moreover, the efficiency of Bakri balloon tamponade alone was not demonstrated clearly in the literature. In most studies, this procedure has been associated with invasive surgery (surgical artery ligation or compressive uterine sutures).

Reply

Patrick Rozenberg — 2013-01-10

We thank Hequet et al for their comments regarding our recent article. We are happy to clarify that our cohort study included only inpatients specifically to avoid a recruitment bias (ie, we did not include patients with severe postpartum hemorrhage who had been referred for embolization from other hospitals in our network). Furthermore, during the first (preballoon) period, we performed embolization only in cases of severe postpartum hemorrhage after vaginal delivery, as indicated in Figure 1 of our article. Severe postpartum hemorrhage during or after cesarean delivery was always treated by conservative surgical procedures or hysterectomy. These important differences explain the reason that our embolization rate was so much lower than that in the French embolization register, as reported by Bartoli et al. We would like to highlight that a major recruitment bias is inherent in this register, which records embolization activity only from referral centers. For example, as Dr Hequet indicates, 80% of the patients treated for postpartum hemorrhage in her referral center come from other hospitals.

Discussion: ‘Ovarian epithelial carcinoma with pelvic endometriosis,’ by Wang et al

2013-03-18

In the roundtable that follows, clinicians discuss a study published in this issue of the Journal in light of its methodology, relevance to practice, and implications for future research. Article discussed:Wang S, Qui L, Lang JH, et al. Clinical analysis of ovarian epithelial carcinoma with coexisting pelvic endometriosis. Am J Obstet Gynecol 2013;208:413.e1-5.

Term delivery following tuboovarian abscess after in vitro fertilization and embryo transfer

Ji Won Kim, Woo Sik Lee, Tae Ki Yoon, Ji Eun Han — 2013-01-28

A tuboovarian abscess (TOA) during pregnancy following oocyte retrieval is extremely rare. We report a rare case of pregnancy complicated by the development of a TOA following in vitro fertilization-embryo transfer that was treated successfully with laparoscopy. We also review all similar cases reported in the English-language literature.

American Journal of Obstetrics & Gynecology

Table of Contents

Information for readers

New tools for an old quest

Patients, providers, and politicians: we all bear the weight of the obesity epidemic

A systematic review of randomized trials assessing human papillomavirus testing in cervical cancer screening

Prenatal treatment of congenital adrenal hyperplasia: risks outweigh benefits

Phenotyping clinical disorders: lessons learned from pelvic organ prolapse

Staged endovascular and surgical treatment of slow-flow vulvar venous malformations

A randomized trial comparing conventional and robotically assisted total laparoscopic hysterectomy

Metabolomic analysis for first-trimester Down syndrome prediction

Recurrence of small-for-gestational-age pregnancy: analysis of first and subsequent singleton pregnancies in The Netherlands

Risk of stillbirth after 37 weeks in pregnancies complicated by small-for-gestational-age fetuses

Maternal seizure disorder and risk of adverse pregnancy outcomes

Seeking the mechanism(s) of action for corticosteroids in HELLP syndrome: SMASH study

Maternal magnesium supplementation reduces intrauterine growth restriction and suppresses inflammation in a rat model

First-trimester detection of fetal anomalies in pregestational diabetes using nuchal translucency, ductus venosus Doppler, and maternal glycosylated hemoglobin

Long-term alterations in maternal plasma proteome after sFlt1–induced preeclampsia in mice

Maternal plasma 25-hydroxyvitamin D levels, angiogenic factors, and preeclampsia

Correction

Significance of growth discordance in appropriately grown twins

DNA methylation at imprint regulatory regions in preterm birth and infection

Down syndrome maternal serum marker screening after 18 weeks of gestation: a countrywide study

Modulation of lipopolysaccharide-induced chorioamnionitis by Ureaplasma parvum in sheep

Safe conception for HIV-discordant couples: insemination with processed semen from the HIV-infected partner

Seasonal variations of human sperm cells among 6455 semen samples: a plausible explanation of a seasonal birth pattern

Correction

Obesity management in gynecologic cancer survivors: provider practices and attitudes

A contemporary analysis of epidemiology and management of vaginal intraepithelial neoplasia

Clinical analysis of ovarian epithelial carcinoma with coexisting pelvic endometriosis

Ovarian epithelial carcinoma with pelvic endometriosis: Wang et al

The case of the sinister spores: The patient was hospitalized for a menacing infection in the second trimester of pregnancy

What is a laborist?

Is early amniotomy in nulliparous labor induction really efficient?

Reply

Trends in the rate of invasive procedures after the addition of the intrauterine tamponade test to a protocol for management of severe postpartum hemorrhage

Reply

Discussion: ‘Ovarian epithelial carcinoma with pelvic endometriosis,’ by Wang et al

Term delivery following tuboovarian abscess after in vitro fertilization and embryo transfer