Journal Cover American Journal of Obstetrics and Gynecology
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   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0002-9378
   Published by Elsevier Homepage  [3177 journals]
  • Meta-analysis on the effect of aspirin use for prevention of preeclampsia
           on placental abruption and antepartum hemorrhage
    • Authors: Stephanie Roberge; Emmanuel Bujold; Kypros H. Nicolaides
      Pages: 483 - 489
      Abstract: Publication date: May 2018
      Source:American Journal of Obstetrics and Gynecology, Volume 218, Issue 5
      Author(s): Stephanie Roberge, Emmanuel Bujold, Kypros H. Nicolaides
      Objective Data Impaired placentation in the first 16 weeks of pregnancy is associated with increased risk of subsequent development of preeclampsia, birth of small-for-gestational-age neonates, and placental abruption. Previous studies reported that prophylactic use of aspirin reduces the risk of preeclampsia and small-for-gestational-age neonates with no significant effect on placental abruption. However, meta-analyses of randomized controlled trials that examined the effect of aspirin in relation to gestational age at onset of therapy and dosage of the drug reported that significant reduction in the risk of preeclampsia and small-for-gestational-age neonates is achieved only if the onset of treatment is at ≤16 weeks of gestation and the daily dosage of the drug is ≥100 mg. Study We aimed to estimate the effect of aspirin on the risk of placental abruption or antepartum hemorrhage in relation to gestational age at onset of therapy and the dosage of the drug. Study Appraisal and Synthesis Methods To perform a systematic review and meta-analysis of randomized controlled trials that evaluated the prophylactic effect of aspirin during pregnancy, we used PubMed, Cinhal, Embase, Web of Science and Cochrane library from 1985 to September 2017. Relative risks of placental abruption or antepartum hemorrhage with their 95% confidence intervals were calculated with the use of random effect models. Analyses were stratified according to daily dose of aspirin (<100 and ≥100 mg) and the gestational age at the onset of therapy (≤16 and >16 weeks of gestation) and compared with the use of subgroup difference analysis. Results The entry criteria were fulfilled by 20 studies on a combined total of 12,585 participants. Aspirin at a dose of <100 mg per day had no impact on the risk of placental abruption or antepartum hemorrhage, irrespective of whether it was initiated at ≤16 weeks of gestation (relative risk, 1.11; 95% confidence interval, 0.52–2.36) or at >16 weeks of gestation (relative risk, 1.32; 95% confidence interval, 0.73–2.39). At ≥100 mg per day, aspirin was not associated with a significant change on the risk of placental abruption or antepartum hemorrhage, whether the treatment was initiated at ≤16 weeks of gestation (relative risk, 0.62, 95% confidence interval, 0.31–1.26), or at >16 weeks of gestation (relative risk, 2.08; 95% confidence interval, 0.86–5.06), but the difference between the subgroups was significant (P=.04). Conclusion Aspirin at a daily dose of ≥100 mg for prevention of preeclampsia that is initiated at ≤16 weeks of gestation, rather than >16 weeks, may decrease the risk of placental abruption or antepartum hemorrhage.

      PubDate: 2018-05-01T14:44:16Z
      DOI: 10.1016/j.ajog.2017.12.238
       
  • Pharmacological treatment of gestational diabetes mellitus:
           point/counterpoint
    • Authors: Oded Langer
      Pages: 490 - 499
      Abstract: Publication date: May 2018
      Source:American Journal of Obstetrics and Gynecology, Volume 218, Issue 5
      Author(s): Oded Langer
      Controversies persist over the most efficacious pharmacologic treatment for gestational diabetes mellitus. For purposes of accuracy in this article, the individual American College of Obstetricians and Gynecologists Practice Bulletin and American Diabetes Association Standards of Medical Care positions on each issue are quoted and then deliberated with evidence of counter claims presented in point/counterpoint. This is a review of all the relevant evidence for the most holistic picture possible. The main issues are (1) which diabetic drugs cross the placenta, (2) the quality of evidence and data source validity, (3) the rationale for the designation of glucose control as the primary outcome in gestational diabetes mellitus, and (4) which drugs (metformin, glyburide, or insulin) are most effective in improving secondary outcomes. The concept that 1 drug fits all, whether it be insulin, glyburide, or metformin, is a fallacy. Different drugs provide certain benefits but not all the benefits and not to all patients. In addition, the steps in the gestational diabetes mellitus management decision path and the current cost of the use of insulin, glyburide, or metformin are addressed. In the future, we must consider studying the potential of diabetic drugs that currently are used in nonpregnancy and incorporating the concept of precision medicine in the decision tree to maximize pregnancy outcomes.

      PubDate: 2018-05-01T14:44:16Z
      DOI: 10.1016/j.ajog.2018.01.024
       
  • Giant cyst of the Nuck canal: a worrisome trouble for a girl
    • Authors: Paolo Sala; Agnese Palmeri; Sergio Costantini
      Pages: 530 - 531
      Abstract: Publication date: May 2018
      Source:American Journal of Obstetrics and Gynecology, Volume 218, Issue 5
      Author(s): Paolo Sala, Agnese Palmeri, Sergio Costantini


      PubDate: 2018-05-01T14:44:16Z
      DOI: 10.1016/j.ajog.2017.12.213
       
  • Laparoscopic vs transvaginal cuff closure after total laparoscopic
           hysterectomy: a randomized trial by the Italian Society of Gynecologic
           Endoscopy
    • Authors: Stefano Uccella; Mario Malzoni; Antonella Cromi; Renato Seracchioli; Giuseppe Ciravolo; Francesco Fanfani; Fevzi Shakir; Salvatore Gueli Alletti; Francesco Legge; Roberto Berretta; Giacomo Corrado; Lucia Casarella; Paolo Donarini; Margherita Zanello; Emanuele Perrone; Baldo Gisone; Enrico Vizza; Giovanni Scambia; Fabio Ghezzi
      Pages: 500.e1 - 500.e13
      Abstract: Publication date: May 2018
      Source:American Journal of Obstetrics and Gynecology, Volume 218, Issue 5
      Author(s): Stefano Uccella, Mario Malzoni, Antonella Cromi, Renato Seracchioli, Giuseppe Ciravolo, Francesco Fanfani, Fevzi Shakir, Salvatore Gueli Alletti, Francesco Legge, Roberto Berretta, Giacomo Corrado, Lucia Casarella, Paolo Donarini, Margherita Zanello, Emanuele Perrone, Baldo Gisone, Enrico Vizza, Giovanni Scambia, Fabio Ghezzi
      Background Vaginal cuff dehiscence following hysterectomy is considered an infrequent but potentially devastating complication. Different possible techniques for cuff closure have been proposed to reduce this threatening adverse event. Objective The aim of the present randomized study was to compare laparoscopic and transvaginal suture of the vaginal vault at the end of a total laparoscopic hysterectomy, in terms of incidence of vaginal dehiscence and vaginal cuff complications. Factors associated with vaginal dehiscence were also analyzed. This article presents the results of the interim analysis of the trial. Study Design Patients undergoing total laparoscopic hysterectomy for benign indications were randomized at the time of colpotomy to receive vaginal closure through transvaginal vs laparoscopic approach using a 1:1 ratio. Allocation concealment was obtained using a password-protected randomization database. Monopolar energy for colpotomy was set at 60W. Vaginal closure was performed with a single-layer running braided and coated 0-polyglactin suture. In all cases an attempt was performed to include the posterior peritoneum in the suture. Laparoscopic knots were tied intracorporeally. All patients were scheduled for a postoperative follow-up visit 3 months after surgery, to detect possible vaginal cuff complications. Univariate and multivariable analyses were performed to identify independent predictors of vaginal cuff dehiscence after total laparoscopic hysterectomy. Results After enrollment of 1408 patients, a prespecified interim analysis was conducted. Thirteen (0.9%) women did not undergo the postoperative assessment and were excluded. Baseline characteristics of the 1395 patients included (695 in the transvaginal group and 700 in the laparoscopic group) were similar between groups. Patients in the transvaginal group had a significantly higher incidence of vaginal dehiscence (2.7% vs 1%; odds ratio, 2.78; 95% confidence interval, 1.16–6.63; P = .01) and of any cuff complication (9.8% vs 4.7%; odds ratio, 2.19; 95% confidence interval, 1.43–3.37; P = .0003). Based on these findings, the data monitoring committee recommended that the trial be terminated early. After multivariable analysis, transvaginal closure of the vault was independently associated with a higher incidence of vaginal dehiscence and any vaginal complication; premenopausal status and smoking habit were independently associated with a higher risk of dehiscence. Conclusion Laparoscopic closure of the vaginal cuff at the end of total laparoscopic hysterectomy is associated with a significant reduction of vaginal dehiscence, any cuff complication, vaginal bleeding, vaginal cuff hematoma, postoperative infection, need for vaginal resuture, and reintervention.

      PubDate: 2018-05-01T14:44:16Z
      DOI: 10.1016/j.ajog.2018.01.029
       
  • A prospective study of the natural history of urinary incontinence in
           women
    • Authors: Kaitlin A. Hagan; Elisabeth Erekson; Andrea Austin; Vatche A. Minassian; Mary K. Townsend; Julie P.W. Bynum; Francine Grodstein
      Pages: 502.e1 - 502.e8
      Abstract: Publication date: May 2018
      Source:American Journal of Obstetrics and Gynecology, Volume 218, Issue 5
      Author(s): Kaitlin A. Hagan, Elisabeth Erekson, Andrea Austin, Vatche A. Minassian, Mary K. Townsend, Julie P.W. Bynum, Francine Grodstein
      Background Symptoms of urinary incontinence are commonly perceived to vary over time; yet, there is limited quantitative evidence regarding the natural history of urinary incontinence, especially over the long term. Objective We sought to delineate the course of urinary incontinence symptoms over time, using 2 large cohorts of middle-aged and older women, with data collected over 10 years. Study Design We studied 9376 women from the Nurses’ Health Study, age 56–81 years at baseline, and 7491 women from the Nurses’ Health Study II, age 39–56 years, with incident urinary incontinence in 2002 through 2003. Urinary incontinence severity was measured by the Sandvik severity index. We tracked persistence, progression, remission, and improvement of symptoms over 10 years. We also examined risk factors for urinary incontinence progression using logistic regression models. Results Among women age 39–56 years, 39% had slight, 45% had moderate, and 17% had severe urinary incontinence at onset. Among women age 56–81 years, 34% had slight, 45% had moderate, and 21% had severe urinary incontinence at onset. Across ages, most women reported persistence or progression of symptoms over follow-up; few (3–11%) reported remission. However, younger women and women with less severe urinary incontinence at onset were more likely to report remission or improvement of symptoms. We found that increasing age was associated with higher odds of progression only among older women (age 75–81 vs 56–60 years; odds ratio, 1.84; 95% confidence interval, 1.51–2.25). Among all women, higher body mass index was strongly associated with progression (younger women: odds ratio, 2.37; 95% confidence interval, 2.00–2.81; body mass index ≥30 vs <25 kg/m2; older women: odds ratio, 1.93; 95% confidence interval, 1.62–2.22). Additionally, greater physical activity was associated with lower odds of progression to severe urinary incontinence (younger women: odds ratio, 0.86; 95% confidence interval, 0.71–1.03; highest vs lowest quartile of activity; older women: odds ratio, 0.68; 95% confidence interval, 0.59–0.80). Conclusion Most women with incident urinary incontinence continued to experience symptoms over 10 years; few had complete remission. Identification of risk factors for urinary incontinence progression, such as body mass index and physical activity, could be important for reducing symptoms over time.

      PubDate: 2018-05-01T14:44:16Z
      DOI: 10.1016/j.ajog.2018.01.045
       
  • Pharmacy-level barriers to implementing expedited partner therapy in
           Baltimore, Maryland
    • Authors: Jennifer Z. Qin; Clarissa P. Diniz; Jenell S. Coleman
      Pages: 504.e1 - 504.e6
      Abstract: Publication date: May 2018
      Source:American Journal of Obstetrics and Gynecology, Volume 218, Issue 5
      Author(s): Jennifer Z. Qin, Clarissa P. Diniz, Jenell S. Coleman
      Background Addressing record high rates of Chlamydia trachomatis incidence in the United States requires the utilization of effective strategies, such as expedited partner therapy, to reduce reinfection and further transmission. Expedited partner therapy, which can be given as a prescription or medication, is a strategy to treat the sexual partners of index patients diagnosed with a sexually transmitted infection without prior medical evaluation of the partners. Objective There are multiple steps in the prescription–expedited partner therapy cascade, and we sought to identify pharmacy-level barriers to implementing prescription–expedited partner therapy for Chlamydia trachomatis treatment. Study Design We used spatial analysis and ArcGIS, a geographic information system, to map and assess geospatial access to pharmacies within Baltimore, MD, neighborhoods with the highest rates of Chlamydia trachomatis (1180.25–4255.31 per 100,000 persons). Expedited partner therapy knowledge and practices were collected via a telephone survey of pharmacists employed at retail pharmacies located in these same neighborhoods. Cost of antibiotic medication in US dollars was collected. Results Census tracts with the highest Chlamydia trachomatis incidence rates had lower median pharmacy density than other census tracts (26.9 per 100,000 vs 31.4 per 100,000, P < .001). We identified 25 pharmacy deserts. Areas defined as pharmacy deserts had larger proportions of black and Hispanic or Latino populations compared with non-Hispanic whites (93.1% vs 6.3%, P < .001) and trended toward higher median Chlamydia trachomatis incidence rates (1170.0 per 100,000 vs 1094.5 per 100,000, P = .110) than non–pharmacy desert areas. Of the 52 pharmacies identified, 96% (50 of 52) responded to our survey. Less than a fifth of pharmacists (18%, 9 of 50) were aware of expedited partner therapy for Chlamydia trachomatis. Most pharmacists (59%, 27 of 46) confirmed they would fill an expedited partner therapy prescription. The cost of a single dose of azithromycin (1 g) ranged from 5.00 to 39.99 US dollars (median, 30 US dollars). Conclusion Limited geographic access to pharmacies, lack of pharmacist awareness of expedited partner therapy, and wide variation in expedited partner therapy medication cost are potential barriers to implementing prescription–expedited partner therapy. Although most Baltimore pharmacists were unaware of expedited partner therapy, they were generally receptive to learning about and filling expedited partner therapy prescriptions. This finding suggests the need for wide dissemination of educational material targeted to pharmacists. In areas with limited geographic access to pharmacies, expedited partner therapy strategies that do not depend on partners physically accessing a pharmacy merit consideration.

      PubDate: 2018-05-01T14:44:16Z
      DOI: 10.1016/j.ajog.2018.01.036
       
  • Cost-effectiveness of emergency contraception options over 1 year
    • Authors: Brandon K. Bellows; Casey R. Tak; Jessica N. Sanders; David K. Turok; Eleanor B. Schwarz
      Pages: 508.e1 - 508.e9
      Abstract: Publication date: May 2018
      Source:American Journal of Obstetrics and Gynecology, Volume 218, Issue 5
      Author(s): Brandon K. Bellows, Casey R. Tak, Jessica N. Sanders, David K. Turok, Eleanor B. Schwarz
      Background The copper intrauterine device is the most effective form of emergency contraception and can also provide long-term contraception. The levonorgestrel intrauterine device has also been studied in combination with oral levonorgestrel for women seeking emergency contraception. However, intrauterine devices have higher up-front costs than oral methods, such as ulipristal acetate and levonorgestrel. Health care payers and decision makers (eg, health care insurers, government programs) with financial constraints must determine if the increased effectiveness of intrauterine device emergency contraception methods are worth the additional costs. Objective We sought to compare the cost-effectiveness of 4 emergency contraception strategies–ulipristal acetate, oral levonorgestrel, copper intrauterine device, and oral levonorgestrel plus same-day levonorgestrel intrauterine device–over 1 year from a US payer perspective. Study Design Costs (2017 US dollars) and pregnancies were estimated over 1 year using a Markov model of 1000 women seeking emergency contraception. Every 28-day cycle, the model estimated the predicted number of pregnancy outcomes (ie, live birth, ectopic pregnancy, spontaneous abortion, or induced abortion) resulting from emergency contraception failure and subsequent contraception use. Model inputs were derived from published literature and national sources. An emergency contraception strategy was considered cost-effective if the incremental cost-effectiveness ratio (ie, the cost to prevent 1 additional pregnancy) was less than the weighted average cost of pregnancy outcomes in the United States ($5167). The incremental cost-effectiveness ratios and probability of being the most cost-effective emergency contraception strategy were calculated from 1000 probabilistic model iterations. One-way sensitivity analyses were used to examine uncertainty in the cost of emergency contraception, subsequent contraception, and pregnancy outcomes as well as the model probabilities. Results In 1000 women seeking emergency contraception, the model estimated direct medical costs of $1,228,000 and 137 unintended pregnancies with ulipristal acetate, compared to $1,279,000 and 150 unintended pregnancies with oral levonorgestrel, $1,376,000 and 61 unintended pregnancies with copper intrauterine devices, and $1,558,000 and 63 unintended pregnancies with oral levonorgestrel plus same-day levonorgestrel intrauterine device. The copper intrauterine device was the most cost-effective emergency contraception strategy in the majority (63.9%) of model iterations and, compared to ulipristal acetate, cost $1957 per additional pregnancy prevented. Model estimates were most sensitive to changes in the cost of the copper intrauterine device (with higher copper intrauterine device costs, oral levonorgestrel plus same-day levonorgestrel intrauterine device became the most cost-effective option) and the cost of a live birth (with lower-cost births, ulipristal acetate became the most cost-effective option). When the proportion of obese women in the population increased, the copper intrauterine device became even more most cost-effective. Conclusion Over 1 year, the copper intrauterine device is currently the most cost-effective emergency contraception option. Policy makers and health care insurance companies should consider the potential for long-term savings when women seeking emergency contraception can promptly obtain whatever contraceptive best meets their personal preferences and needs; this will require removing barriers and promoting access to intrauterine devices at emergency contraception visits.

      PubDate: 2018-05-01T14:44:16Z
      DOI: 10.1016/j.ajog.2018.01.025
       
  • Structural, functional, and symptomatic differences between women with
           rectocele versus cystocele and normal support
    • Authors: Mitchell B. Berger; Giselle E. Kolenic; Dee E. Fenner; Daniel M. Morgan; John O.L. DeLancey
      Pages: 510.e1 - 510.e8
      Abstract: Publication date: May 2018
      Source:American Journal of Obstetrics and Gynecology, Volume 218, Issue 5
      Author(s): Mitchell B. Berger, Giselle E. Kolenic, Dee E. Fenner, Daniel M. Morgan, John O.L. DeLancey
      Background Prolapse of the anterior and posterior vaginal walls has been generally associated with apical descent and levator ani muscle defects. However, the relative contributions of these factors to the pathophysiology of descent in the different vaginal compartments is not well understood. Furthermore, symptoms uniquely associated with prolapse in these compartments have not been well characterized. Objectives The objectives of the study were to compare the associations between the following: (1) apical support, (2) levator ani muscles, and (3) pelvic floor symptoms in women with posterior-predominant prolapse, anterior-predominant prolapse, and normal support. Study Design This is a cross-sectional study with 2 case arms: 60 women with posterior prolapse, 90 with anterior prolapse, and a referent control arm with 103 asymptomatic subjects with normal support, determined from pelvic organ prolapse quantification examinations. Levator muscle defects were graded from magnetic resonance imaging. Vaginal closure forces above resting were measured with an instrumented speculum during maximal contraction. Pelvic floor symptoms were measured via the Pelvic Floor Distress Inventory–Short Form. Results Mean point C location in controls was –6.9 cm [1.5] (mean [standard deviation]); and was higher in posterior prolapse (–4.7 cm [2.7], 2.2 cm below controls) than the anterior prolapse group (–1.2 cm [4.1]; 5.6 cm below controls, P < .001 for all comparisons). Normal-appearing muscles (ie, muscle without a visible defect) occurred at similar frequencies in posterior prolapse (45%) and controls (51%, P = .43) but less often in anterior prolapse (28%, P ≤ .03 for pairwise comparisons). Major levator ani defects occurred at similar rates in women with posterior (33%) and anterior prolapse (42%, P = .27) but less often in controls (16%, P ≤ .012 for both pairwise comparisons). Similarly, there were significant differences in generated vaginal closure forces across the 3 groups, with the prolapse groups generating weaker closure forces than the control group (P = .004), but the differences between the 2 prolapse groups were not significant after controlling for prolapse size (P = .43). Pelvic floor symptoms were more severe for the posterior (mean Pelvic Floor Distress Inventory score, 129) and anterior prolapse groups (score, 128) than the controls (score, 40.2, P < .001 for both comparisons); the difference between the 2 prolapse groups was not significant (P = .83). Conclusion Posterior-predominant prolapse involves an almost 3-fold less apical descent below normal than anterior-predominant vaginal prolapse. Levator ani defects and muscle impairment also have a lower impact. Pelvic floor symptoms reflect the presence and size of prolapse more than the predominant lax vaginal compartment.

      PubDate: 2018-05-01T14:44:16Z
      DOI: 10.1016/j.ajog.2018.01.033
       
  • Pelvic muscles’ mechanical response to strains in the absence and
           presence of pregnancy-induced adaptations in a rat model
    • Authors: Tatiana Catanzarite; Shannon Bremner; Caitlin L. Barlow; Laura Bou-Malham; Shawn O’Connor; Marianna Alperin
      Pages: 512.e1 - 512.e9
      Abstract: Publication date: May 2018
      Source:American Journal of Obstetrics and Gynecology, Volume 218, Issue 5
      Author(s): Tatiana Catanzarite, Shannon Bremner, Caitlin L. Barlow, Laura Bou-Malham, Shawn O’Connor, Marianna Alperin
      Background Maternal birth trauma to the pelvic floor muscles is thought to be consequent to mechanical demands placed on these muscles during fetal delivery that exceed muscle physiological limits. The above is consistent with studies of striated limb muscles that identify hyperelongation of sarcomeres, the functional muscle units, as the primary cause of mechanical muscle injury and resultant muscle dysfunction. However, pelvic floor muscles’ mechanical response to strains have not been examined at a tissue level. Furthermore, we have previously demonstrated that during pregnancy, rat pelvic floor muscles acquire structural and functional adaptations in preparation for delivery, which likely protect against mechanical muscle injury by attenuating the strain effect. Objective We sought to determine the mechanical impact of parturition-related strains on pelvic floor muscles’ microstructure, and test the hypothesis that pregnancy-induced adaptations modulate muscle response to strains associated with vaginal delivery. Study Design Three-month-old Sprague-Dawley late-pregnant (N = 20) and nonpregnant (N = 22) rats underwent vaginal distention, replicating fetal crowning, with variable distention volumes. Age-matched uninjured pregnant and nonpregnant rats served as respective controls. After sacrifice, pelvic floor muscles, which include coccygeus, iliocaudalis, and pubocaudalis, were fixed in situ and harvested for fiber and sarcomere length measurements. To ascertain the extent of physiological strains during spontaneous vaginal delivery, analogous measurements were obtained in intrapartum rats (N = 4) sacrificed during fetal delivery. Data were compared with repeated measures and 2-way analysis of variance, followed by pairwise comparisons, with significance set at P < .05. Results Gross anatomic changes were observed in the pelvic floor muscles following vaginal distention, particularly in the entheseal region of pubocaudalis, which appeared translucent. The above appearance resulted from dramatic stretch of the myofibers, as indicated by significantly longer fiber length compared to controls. Stretch ratios, calculated as fiber length after vaginal distention divided by baseline fiber length, increased gradually with increasing distention volume. Paralleling these macroscopic changes, vaginal distention resulted in acute and progressive increase in sarcomere length with rising distention volume. The magnitude of strain effect varied by muscle, with the greatest sarcomere elongation observed in coccygeus, followed by pubocaudalis, and a smaller increase in iliocaudalis, observed only at higher distention volumes. The average fetal rat volume approximated 3 mL. Pelvic floor muscle sarcomere lengths in pregnant animals undergoing vaginal distention with 3 mL were similar to intrapartum sarcomere lengths in all muscles (P > .4), supporting the validity of our experimental approach. Vaginal distention resulted in dramatically longer sarcomere lengths in nonpregnant compared to pregnant animals, especially in coccygeus and pubocaudalis (P < .0001), indicating significant attenuation of sarcomere elongation in the presence of pregnancy-induced adaptations in pelvic floor muscles. Conclusion Delivery-related strains lead to acute sarcomere elongation, a well-established cause of mechanical injury in skeletal muscles. Sarcomere hyperelongation resultant from mechanical strains is attenuated by pregnancy-induced adaptations acquired by the pelvic floor muscles prior to parturition.

      PubDate: 2018-05-01T14:44:16Z
      DOI: 10.1016/j.ajog.2018.02.001
       
  • Early and late preeclampsia are characterized by high cardiac output, but
           in the presence of fetal growth restriction, cardiac output is low:
           insights from a prospective study
    • Authors: Jasmine Tay; Lin Foo; Giulia Masini; Phillip R. Bennett; Carmel M. McEniery; Ian B. Wilkinson; Christoph C. Lees
      Pages: 517.e1 - 517.e12
      Abstract: Publication date: May 2018
      Source:American Journal of Obstetrics and Gynecology, Volume 218, Issue 5
      Author(s): Jasmine Tay, Lin Foo, Giulia Masini, Phillip R. Bennett, Carmel M. McEniery, Ian B. Wilkinson, Christoph C. Lees
      Background Preeclampsia and fetal growth restriction are considered to be placentally mediated disorders. The clinical manifestations are widely held to relate to gestation age at onset with early- and late-onset preeclampsia considered to be phenotypically distinct. Recent studies have reported conflicting findings in relation to cardiovascular function, and in particular cardiac output, in preeclampsia and fetal growth restriction. Objective We conducted this study to examine the possible relation between cardiac output and peripheral vascular resistance in preeclampsia and fetal growth restriction. Study Design We investigated maternal cardiovascular function in relation to clinical subtype in 45 pathological pregnancies (14 preeclampsia only, 16 fetal growth restriction only, 15 preeclampsia and fetal growth restriction) and compared these with 107 healthy person observations. Cardiac output was the primary outcome measure and was assessed using an inert gas-rebreathing method (Innocor), from which peripheral vascular resistance was derived; arterial function was assessed by Vicorder, a cuff-based oscillometric device. Cardiovascular parameters were normalized for gestational age in relation to healthy pregnancies using Z scores, thus allowing for comparison across the gestational range of 24–40 weeks. Results Compared with healthy control pregnancies, women with preeclampsia had higher cardiac output Z scores (1.87 ± 1.35; P = .0001) and lower peripheral vascular resistance Z scores (–0.76 ± 0.89; P = .025); those with fetal growth restriction had higher peripheral vascular resistance Z scores (0.57 ± 1.18; P = .04) and those with both preeclampsia and fetal growth restriction had lower cardiac output Z scores (–0.80 ± 1.3 P = .007) and higher peripheral vascular resistance Z scores (2.16 ± 1.96; P = .0001). These changes were not related to gestational age of onset. All those affected by preeclampsia and/or fetal growth restriction had abnormally raised augmentation index and pulse wave velocity. Furthermore, in preeclampsia, low cardiac output was associated with low birthweight and high cardiac output with high birthweight (r = 0.42, P = .03). Conclusion Preeclampsia is associated with high cardiac output, but if preeclampsia presents with fetal growth restriction, the opposite is true; both conditions are nevertheless defined by hypertension. Fetal growth restriction without preeclampsia is associated with high peripheral vascular resistance. Although early and late gestation preeclampsias are considered to be different diseases, we show that the hemodynamic characteristics of preeclampsia were unrelated to gestational age at onset but were strongly associated with the presence or absence of fetal growth restriction. Fetal growth restriction more commonly coexists with preeclampsia at early gestation, thus explaining the conflicting results of previous studies. Furthermore, antihypertensive agents act by reducing cardiac output or peripheral vascular resistance and are administered without reference to cardiovascular function in preeclampsia. The underlying pathology (preeclampsia, fetal growth restriction, preeclampsia and fetal growth restriction) defines cardiovascular phenotype, providing a rational basis for choice of therapy in which high or low cardiac output or peripheral vascular resistance is the predominant feature.

      PubDate: 2018-05-01T14:44:16Z
      DOI: 10.1016/j.ajog.2018.02.007
       
  • Predictors of sleep-disordered breathing in pregnancy
    • Authors: Judette M. Louis; Matthew A. Koch; Uma M. Reddy; Robert M. Silver; Corette B. Parker; Francesca L. Facco; Susan Redline; Chia-Ling Nhan-Chang; Judith H. Chung; Grace W. Pien; Robert C. Basner; William A. Grobman; Deborah A. Wing; Hyagriv N. Simhan; David M. Haas; Brian M. Mercer; Samuel Parry; Daniel Mobley; Benjamin Carper; George R. Saade; Frank P. Schubert; Phyllis C. Zee
      Pages: 521.e1 - 521.e12
      Abstract: Publication date: May 2018
      Source:American Journal of Obstetrics and Gynecology, Volume 218, Issue 5
      Author(s): Judette M. Louis, Matthew A. Koch, Uma M. Reddy, Robert M. Silver, Corette B. Parker, Francesca L. Facco, Susan Redline, Chia-Ling Nhan-Chang, Judith H. Chung, Grace W. Pien, Robert C. Basner, William A. Grobman, Deborah A. Wing, Hyagriv N. Simhan, David M. Haas, Brian M. Mercer, Samuel Parry, Daniel Mobley, Benjamin Carper, George R. Saade, Frank P. Schubert, Phyllis C. Zee
      Background Sleep-disordered breathing (SDB) is common in pregnancy, but there are limited data on predictors. Objectives The objective of this study was to develop predictive models of sleep-disordered breathing during pregnancy. Study Design Nulliparous women completed validated questionnaires to assess for symptoms related to snoring, fatigue, excessive daytime sleepiness, insomnia, and restless leg syndrome. The questionnaires included questions regarding the timing of sleep and sleep duration, work schedules (eg, shift work, night work), sleep positions, and previously diagnosed sleep disorders. Frequent snoring was defined as self-reported snoring ≥3 days per week. Participants underwent in-home portable sleep studies for sleep-disordered breathing assessment in early (6–15 weeks gestation) and mid pregnancy (22–31 weeks gestation). Sleep-disordered breathing was characterized by an apnea hypopnea index that included all apneas, plus hypopneas with ≥3% oxygen desaturation. For primary analyses, an apnea hypopnea index ≥5 events per hour was used to define sleep-disordered breathing. Odds ratios and 95% confidence intervals were calculated for predictor variables. Predictive ability of the logistic models was estimated with area under the receiver-operating-characteristic curves, along with sensitivities, specificities, and positive and negative predictive values and likelihood ratios. Results Among 3705 women who were enrolled, data were available for 3264 and 2512 women in early and mid pregnancy, respectively. The corresponding prevalence of sleep-disordered breathing was 3.6% and 8.3%, respectively. At each time point in gestation, frequent snoring, chronic hypertension, greater maternal age, body mass index, neck circumference, and systolic blood pressure were associated most strongly with an increased risk of sleep-disordered breathing. Logistic regression models that included current age, body mass index, and frequent snoring predicted sleep-disordered breathing in early pregnancy, sleep-disordered breathing in mid pregnancy, and new onset sleep-disordered breathing in mid pregnancy with 10-fold cross-validated area under the receiver-operating-characteristic curves of 0.870, 0.838, and 0.809. We provide a supplement with expanded tables, integrated predictiveness, classification curves, and an predicted probability calculator. Conclusion Among nulliparous pregnant women, logistic regression models with just 3 variables (ie, age, body mass index, and frequent snoring) achieved good prediction of prevalent and incident sleep-disordered breathing. These results can help with screening for sleep-disordered breathing in the clinical setting and for future clinical treatment trials.

      PubDate: 2018-05-01T14:44:16Z
      DOI: 10.1016/j.ajog.2018.01.031
       
  • In vivo Raman spectroscopy for biochemical monitoring of the human
           cervix throughout pregnancy
    • Authors: Christine M. O’Brien; Elizabeth Vargis; Amy Rudin; James C. Slaughter; Giju Thomas; J Michael Newton; Jeff Reese; Kelly A. Bennett; Anita Mahadevan-Jansen
      Pages: 528.e1 - 528.e18
      Abstract: Publication date: May 2018
      Source:American Journal of Obstetrics and Gynecology, Volume 218, Issue 5
      Author(s): Christine M. O’Brien, Elizabeth Vargis, Amy Rudin, James C. Slaughter, Giju Thomas, J Michael Newton, Jeff Reese, Kelly A. Bennett, Anita Mahadevan-Jansen
      Background The cervix must undergo significant biochemical remodeling to allow for successful parturition. This process is not fully understood, especially in instances of spontaneous preterm birth. In vivo Raman spectroscopy is an optical technique that can be used to investigate the biochemical composition of tissue longitudinally and noninvasively in human beings, and has been utilized to measure physiology and disease states in a variety of medical applications. Objective The purpose of this study is to measure in vivo Raman spectra of the cervix throughout pregnancy in women, and to identify biochemical markers that change with the preparation for delivery and postpartum repair. Study Design In all, 68 healthy pregnant women were recruited. Raman spectra were measured from the cervix of each patient monthly in the first and second trimesters, weekly in the third trimester, and at the 6-week postpartum visit. Raman spectra were measured using an in vivo Raman system with an optical fiber probe to excite the tissue with 785 nm light. A spectral model was developed to highlight spectral regions that undergo the most changes throughout pregnancy, which were subsequently used for identifying Raman peaks for further analysis. These peaks were analyzed longitudinally to determine if they underwent significant changes over the course of pregnancy (P < .05). Finally, 6 individual components that comprise key biochemical constituents of the human cervix were measured to extract their contributions in spectral changes throughout pregnancy using a linear combination method. Patient factors including body mass index and parity were included as variables in these analyses. Results Raman peaks indicative of extracellular matrix proteins (1248 and 1254 cm−1) significantly decreased (P < .05), while peaks corresponding to blood (1233 and 1563 cm–1) significantly increased (P < .0005) in a linear manner throughout pregnancy. In the postpartum cervix, significant increases in peaks corresponding to actin (1003, 1339, and 1657 cm–1) and cholesterol (1447 cm–1) were observed when compared to late gestation, while signatures from blood significantly decreased. Postpartum actin signals were significantly higher than early pregnancy, whereas extracellular matrix proteins and water signals were significantly lower than early weeks of gestation. Parity had a significant effect on blood and extracellular matrix protein signals, with nulliparous patients having significant increases in blood signals throughout pregnancy, and higher extracellular matrix protein signals in early pregnancy compared to patients with prior pregnancies. Body mass index significantly affected actin signal contribution, with low body mass index patients showing decreasing actin contribution throughout pregnancy and high body mass index patients demonstrating increasing actin signals. Conclusion Raman spectroscopy was successfully used to biochemically monitor cervical remodeling in pregnant women during prenatal visits. This foundational study has demonstrated sensitivity to known biochemical dynamics that occur during cervical remodeling, and identified patient variables that have significant effects on Raman spectra throughout pregnancy. Raman spectroscopy has the potential to improve our understanding of cervical maturation, and be used as a noninvasive preterm birth risk assessment tool to reduce the incidence, morbidity, and mortality caused by preterm birth.

      PubDate: 2018-05-01T14:44:16Z
      DOI: 10.1016/j.ajog.2018.01.030
       
  • Hormonal contraception and breast cancer
    • Authors: Carolyn L. Westhoff; Malcolm C. Pike
      Abstract: Publication date: Available online 17 May 2018
      Source:American Journal of Obstetrics and Gynecology
      Author(s): Carolyn L. Westhoff, Malcolm C. Pike
      The recent Danish cohort study reported a 20% increased risk of breast cancer among current and recent hormonal contraception users. These results are largely consistent with previous studies. This study did not report on stage of disease at diagnosis and it is not clear to what extent the apparent increased risk may be due to a small advance in the timing of diagnosis. This study did not report on the risk associated with the use of a 20-μg ethinyl estradiol pill. They did find an increasing risk in current users of longer duration and an increased risk with use of the levonorgestrel intrauterine system–both of these potentially important findings have not been consistently found in previous studies and require further investigation. The breast cancer effects described now in multiple studies wane with time, and in the long-term hormonal contraception use has been found not to be associated with any increased total cancer risk.

      PubDate: 2018-05-18T16:00:48Z
      DOI: 10.1016/j.ajog.2018.03.032
       
  • Early prognostic factors of outcomes in monochorionic twin pregnancy:
           systematic review and meta-analysis
    • Authors: Fiona L. Mackie; Matthew J. Hall; R. Katie Morris; Mark D. Kilby
      Abstract: Publication date: Available online 12 May 2018
      Source:American Journal of Obstetrics and Gynecology
      Author(s): Fiona L. Mackie, Matthew J. Hall, R. Katie Morris, Mark D. Kilby
      Objective Assess ability of first trimester pregnancy related factors (ultrasound measurements, maternal characteristics, biomarkers) to predict complications in monochorionic twin pregnancies Data sources MEDLINE, EMBASE, ISI Web of Science, CINAHL, the Cochrane Central Registration of Controlled Trials and Research Registers, and Google Scholar, from inception to 12 May 2017. Grey literature and bibliographies of articles were checked. Study eligibility criteria Studies that reported ultrasound measurements, maternal characteristics, or potential biomarkers, measured in the first trimester in monochorionic diamniotic twin pregnancies, where the potential prognostic ability between the variable and twin-twin transfusion syndrome, growth restriction, or intrauterine fetal death could be assessed. Study appraisal and synthesis methods Quality assessment was evaluated using the STROBE checklist by 2 reviewers independently. For meta-analysis, odds ratios using a random effects model, or standardized mean difference were calculated. If a moderate association was found, the prognostic ability was evaluated by calculating the sensitivity and specificity. Risk of heterogeneity was reported as I2 and publication bias was visually assessed by funnel plots and quantitatively by Egger’s test. Results Forty-eight studies were eligible for inclusion. Twenty meta-analyses could be performed. A moderate association was demonstrated in 3 meta-analyses, between: NT>95th centile in one/both fetuses and TTTS (OR 2.29 [95%CI 1.05, 4.96] I2=6.6%, 4 studies, 615 pregnancies); CRL discordance ≥10% and TTTS (OR 2.43 [95%CI 1.13, 5.21] I2=14.1%, 3 studies, 708 pregnancies); and maternal ethnicity and TTTS (OR 2.12 [95%CI 1.17, 3.83] I2=0.0%, 5 studies, 467 pregnancies), but none demonstrated a prognostic ability for any outcome under investigation. Conclusions It is not currently possible to predict adverse outcomes in monochorionic twin pregnancies. We have revealed a lack of research investigating first trimester biomarkers in monochorionic twin pregnancies. Different assessment methods and definitions of each variable and outcome were an issue and this highlights the need for a large cohort study to evaluate these factors.

      PubDate: 2018-05-18T16:00:48Z
      DOI: 10.1016/j.ajog.2018.05.008
       
  • The efficacy of antenatal steroid therapy is dependent on the duration of
           low-concentration fetal exposure: Evidence from a sheep model of pregnancy
           
    • Authors: Matthew W. Kemp; Masatoshi Saito; Haruo Usuda; Shimpei Watanabe; Shinichi Sato; Takushi Hanita; Yusaku Kumagai; Timothy J. Molloy; Michael Clarke; Peter J. Eddershaw; Gabrielle C. Musk; Augusto Schmidt; Demelza Ireland; Lucy Furfaro; Matthew S. Payne; John P. Newnham; Alan H. Jobe
      Abstract: Publication date: Available online 11 May 2018
      Source:American Journal of Obstetrics and Gynecology
      Author(s): Matthew W. Kemp, Masatoshi Saito, Haruo Usuda, Shimpei Watanabe, Shinichi Sato, Takushi Hanita, Yusaku Kumagai, Timothy J. Molloy, Michael Clarke, Peter J. Eddershaw, Gabrielle C. Musk, Augusto Schmidt, Demelza Ireland, Lucy Furfaro, Matthew S. Payne, John P. Newnham, Alan H. Jobe
      Objective Antenatal corticosteroids (ANS) are among the most important and widely used interventions to improve outcomes for preterm infants. ANS dosing regimens remain un-optimized and without maternal weight-adjusted dosing. We, and others, have hypothesised that once a low concentration of materno-fetal steroid exposure is achieved and maintained, the duration of the steroid exposure determines treatment efficacy. Using a sheep model of pregnancy, we tested the relationship between steroid dose, and duration of exposure, and treatment efficacy. Methods Ewes with single fetuses at 120 d gestation received an intravenous bolus (loading dose) followed by a maintenance infusion of betamethasone phosphate to target 12 hour fetal plasma betamethasone concentrations of either: i) 20 ng/mL; ii) 10 ng/mL; or iii) 2 ng/mL. In a subsequent experiment, fetal plasma betamethasone concentrations were targeted at 2 ng/mL for 26 hours. Negative control animals received sterile saline. Positive control animals received two intramuscular injections of 0.25 mg/kg Celestone® Chronodose® (betamethasone phosphate + betamethasone acetate) spaced at 24 hours. Preterm lambs were surgically delivered and ventilated 48 hours after treatment commenced. Maternal and fetal plasma betamethasone concentrations were confirmed by mass spectrometry in a parallel study of chronically-catheterized, corticosteroid-treated ewes and fetuses. Results The loading and maintenance doses were achieved, and maintained the desired fetal plasma betamethasone concentrations of approximately 20, 10 and 2 ng/mL for 12 hours. Compared with the 12 hour infusion-treated animals, lambs from the positive control (2 intramuscular doses of 0.25 mg/kg Celestone® Chronodose®) group had the greatest functional lung maturation (compliance, gas exchange, arterial pH) and molecular evidence of maturation (glucocorticoid receptor signalling activation), despite having maximum fetal plasma betamethasone concentrations 2.5 x lower than animals in the 20 ng/mL betamethasone infusion group. Lambs from the 12 hour 2ng/mL betamethasone infusion group had little functional lung maturation. In contrast, lambs from the 26 hour 2 ng/mL betamethasone infusion group had functional lung maturation equivalent to lambs from the positive control group. Conclusion In preterm lambs exposed to ANS, high materno-fetal plasma betamethasone concentrations did not correlate with improved lung maturation. The largest and most consistent improvements in lung maturation were in animals exposed to either the clinical course of Celestone® Chronodose® or a low-dose betamethasone phosphate infusion to achieve a fetal plasma betamethasone concentration of approximately 2 ng/mL for 26 h. The duration of low-concentration materno-fetal steroid exposure, not total dose or peak drug exposure, is a key determinant for ANS efficacy. These findings underscore the need to develop an optimised steroid dosing regimen that may improve both the efficacy and safety of ANS therapy.

      PubDate: 2018-05-18T16:00:48Z
      DOI: 10.1016/j.ajog.2018.05.007
       
  • Prediction calculator for induction of labor: no Holy Grail yet!
    • Authors: Sepand Alavifard; Kennedy Meier; Rohan D’Souza
      Abstract: Publication date: Available online 9 May 2018
      Source:American Journal of Obstetrics and Gynecology
      Author(s): Sepand Alavifard, Kennedy Meier, Rohan D’Souza


      PubDate: 2018-05-18T16:00:48Z
      DOI: 10.1016/j.ajog.2018.04.060
       
  • Letter to the Editor On: A validated calculator to estimate risk of
           cesarean after an induction of labor with an unfavorable cervix
    • Authors: Cynthia Abraham
      Abstract: Publication date: Available online 9 May 2018
      Source:American Journal of Obstetrics and Gynecology
      Author(s): Cynthia Abraham


      PubDate: 2018-05-18T16:00:48Z
      DOI: 10.1016/j.ajog.2018.04.053
       
  • Reply to Letter L18-017AR1, L18-024AR1, and L18-026A_updated regarding
           manuscript entitled: “A validated calculator to estimate risk of
           cesarean after an induction of labor with an unfavorable cervix”
    • Authors: Lisa D. Levine; Katheryne L. Downes
      Abstract: Publication date: Available online 9 May 2018
      Source:American Journal of Obstetrics and Gynecology
      Author(s): Lisa D. Levine, Katheryne L. Downes


      PubDate: 2018-05-18T16:00:48Z
      DOI: 10.1016/j.ajog.2018.04.057
       
  • Reply to Dr. Matsubara
    • Authors: Brett D. Einerson; Christina E. Rodriguez; Robert M. Silver
      Abstract: Publication date: Available online 9 May 2018
      Source:American Journal of Obstetrics and Gynecology
      Author(s): Brett D. Einerson, Christina E. Rodriguez, Robert M. Silver


      PubDate: 2018-05-18T16:00:48Z
      DOI: 10.1016/j.ajog.2018.04.056
       
  • Letter to the Editor
    • Authors: Mark G. Doherty
      Abstract: Publication date: Available online 9 May 2018
      Source:American Journal of Obstetrics and Gynecology
      Author(s): Mark G. Doherty


      PubDate: 2018-05-18T16:00:48Z
      DOI: 10.1016/j.ajog.2018.04.054
       
  • Magnetic resonance imaging for diagnosis of placenta accreta spectrum
           disorders: Still useful for real-world practice
    • Authors: Shigeki Matsubara; Hironori Takahashi; Yuji Takei
      Abstract: Publication date: Available online 9 May 2018
      Source:American Journal of Obstetrics and Gynecology
      Author(s): Shigeki Matsubara, Hironori Takahashi, Yuji Takei


      PubDate: 2018-05-18T16:00:48Z
      DOI: 10.1016/j.ajog.2018.04.058
       
  • Reply to Letter # “L18-047AR1”
    • Authors: Antoinette T. Nguyen; Khadijah Z. Bhatti; Gretchen S. Stuart
      Abstract: Publication date: Available online 9 May 2018
      Source:American Journal of Obstetrics and Gynecology
      Author(s): Antoinette T. Nguyen, Khadijah Z. Bhatti, Gretchen S. Stuart


      PubDate: 2018-05-18T16:00:48Z
      DOI: 10.1016/j.ajog.2018.04.055
       
  • The Comparing Options for Management: Patient-centered Results for Uterine
           Fibroids (COMPARE-UF) Registry: Rationale and Design
    • Authors: Elizabeth A. Stewart; Barbara L. Lytle; Laine Thomas; Ganesa R. Wegienka; Vanessa Jacoby; Michael P. Diamond; Wanda K. Nicholson; Raymond M. Anchan; Sateria Venable; Kedra Wallace; Erica E. Marsh; George L. Maxwell; Bijan J. Borah; William H. Catherino; Evan R. Myers
      Abstract: Publication date: Available online 8 May 2018
      Source:American Journal of Obstetrics and Gynecology
      Author(s): Elizabeth A. Stewart, Barbara L. Lytle, Laine Thomas, Ganesa R. Wegienka, Vanessa Jacoby, Michael P. Diamond, Wanda K. Nicholson, Raymond M. Anchan, Sateria Venable, Kedra Wallace, Erica E. Marsh, George L. Maxwell, Bijan J. Borah, William H. Catherino, Evan R. Myers
      Objective To design and establish a uterine fibroid (UF) registry based in the United States (US) to provide comparative effectiveness data regarding UF treatment. Study Design We report here the design and initial recruitment for the Comparing Options for Management: Patient-centered Results for Uterine Fibroids (COMPARE-UF) registry (Clinicaltrials.gov, NCT02260752), funded by the Agency for Healthcare Research and Quality (AHRQ) in collaboration with the-Patient-Centered Outcomes Research Institute (PCORI). COMPARE-UF is designed to help answer critical questions about treatment options for women with symptomatic UF. Women undergoing a procedure for UF (hysterectomy, myomectomy [abdominal, hysteroscopic, vaginal and laparoscopic/robotic], endometrial ablation, radiofrequency fibroid ablation, uterine artery embolization, magnetic resonance guided focused ultrasound or progestin-releasing intrauterine device insertion) at one of the COMPARE-UF sites are invited to participate in a prospective registry with three years follow-up for post-procedural outcomes. Enrolled participants provide annual follow-up through an online portal or through traditional phone contact. A central data abstraction center provides information obtained from imaging, operative or procedural notes and pathology reports. Women with uterine fibroids and other stakeholders are a key part of the COMPARE-UF registry and participate at all points from study design to dissemination of results. Results We built a network of nine clinical sites across the US with expertise in the care of women with UF to capture geographic, racial, ethnic and procedural diversity. Of the initial 2031 women enrolled in COMPARE-UF, 42% are self-identified as Black or African-American and 40% are age 40 years or younger with 16% of participants under age 35. Women undergoing myomectomy comprise the largest treatment group at 46% of all procedures with laparoscopic or robotic myomectomy comprising the largest subset of myomectomies at 19% of all procedures. Hysterectomy is the second most common treatment within the registry at 38%. Conclusions In response to priorities identified by our patient stakeholders, the initial aims within COMPARE-UF will address how different procedures used to treat UF compare in terms of long-lasting symptom relief, potential for recurrence, medical complications, improvement in quality of life and sexual function, age at menopause, and fertility and pregnancy outcomes. COMPARE-UF will generate evidence on the comparative effectiveness of different procedural options for UF, in order to help patients and their caregivers make informed decisions that best meet an individual patient’s short- and long-term preferences. Building upon this infrastructure, the COMPARE-UF team of investigators and stakeholders, including patients, collaborate to identify future priorities for expanding the registry, such assessing the efficacy of medical therapies for UF. COMPARE-UF results will be disseminated directly to patients, providers, and other stakeholders using traditional academic pathways, as well as innovative methods, including a variety of social media platforms. Given demographic differences among women undergoing different UF treatments, assessing comparative effectiveness for this disease through clinical trials will remain difficult. Therefore, this registry provides optimized evidence to help patients and their providers better understand the pros and cons of different treatment options so that they can make more informed decisions.

      PubDate: 2018-05-18T16:00:48Z
      DOI: 10.1016/j.ajog.2018.05.004
       
  • Non-invasive estimation of fetal lung maturity using magnetic resonance
           spectroscopy
    • Authors: Stefan Bluml; Vidya Rajagopalan
      Abstract: Publication date: Available online 8 May 2018
      Source:American Journal of Obstetrics and Gynecology
      Author(s): Stefan Bluml, Vidya Rajagopalan


      PubDate: 2018-05-18T16:00:48Z
      DOI: 10.1016/j.ajog.2018.04.043
       
  • Concerns regarding a validated calculator to estimate risk of cesarean
           after an induction of labor with an unfavorable cervix
    • Authors: Gustavo A. San Román
      Abstract: Publication date: Available online 8 May 2018
      Source:American Journal of Obstetrics and Gynecology
      Author(s): Gustavo A. San Román


      PubDate: 2018-05-18T16:00:48Z
      DOI: 10.1016/j.ajog.2018.04.061
       
  • Modulation of nuclear factor-κB signaling and reduction of neural tube
           defects by quercetin-3-glucoside in embryos of diabetic mice
    • Authors: Chengyu Tan; Fantong Meng; E. Albert Reece; Zhiyong Zhao
      Abstract: Publication date: Available online 5 May 2018
      Source:American Journal of Obstetrics and Gynecology
      Author(s): Chengyu Tan, Fantong Meng, E. Albert Reece, Zhiyong Zhao
      Background Diabetes mellitus in early pregnancy increases the risk of birth defects in infants. Maternal hyperglycemia stimulates the expression of nitric oxide (NO) synthase 2 (NOS2), which can be regulated by transcription factors of the nuclear factor-κB (NF-κB) family. Increases in reactive nitrogen species (RNS) generate intracellular stress conditions, including nitrosative, oxidative, and endoplasmic reticulum (ER) stresses, and trigger programmed cell death (or apoptosis) in the neural folds, resulting in neural tube defects (NTDs) in the embryo. Inhibiting NOS2 can reduce NTDs; however, the underlying mechanisms require further delineation. Targeting NOS2 and associated nitrosative stress using naturally occurring phytochemicals is a potential approach to preventing birth defects in diabetic pregnancies. Objectives This study aims to investigate the effect of quercetin-3-glucoside (Q3G), a polyphenol flavonoid found in fruit, in reducing maternal diabetes-induced NTDs in an animal model, and to delineate the molecular mechanisms underlying Q3G action in regulating NOS2 expression. Study Design Female mice (C57BL/6) were induced to develop diabetes using streptozotocin before pregnancy. Diabetic pregnant mice were administered Q3G (100 mg/kg) daily via gavage feeding, introduction of drug to the stomach directly via a feeding needle, during neurulation from embryonic (E) day 6.5 to E9.5. After treatment, E10.5 embryos were collected and examined for the presence of NTDs and apoptosis in the neural tube. Expression of Nos2 and superoxide dismutase 1 (Sod1; an antioxidative enzyme) was quantified using Western blot assay. Nitrosative, oxidative, and endoplasmic reticulum (ER) stress conditions were assessed using specific biomarkers. Expression and posttranslational modification of factors in the NF-κB system were investigated. Results Treatment with Q3G (suspended in water) significantly decreased NTD rate (24.7%) and apoptosis in the embryos of diabetic mice, compared with those in the water-treated diabetic group (3.1%; p<0.001). Q3G decreased the expression of Nos2 and nitrosative stress (p<0.05). It also increased the levels of Sod1 (p<0.05), further increasing the antioxidative capacity of the cells. Q3G treatment also alleviated of ER stress in the embryos of diabetic mice (p<0.05). Q3G reduced the levels of p65 (RelA; p<0.05), a member of the NF-κB transcription factor family, but augmented the levels of the inhibitor of κBα (IκBα; p<0.05), which suppresses p65 nuclear translocation. In association with these changes, the levels of IκB kinase α (Ikkα) and IκBα phosphorylation were elevated (p<0.05). Conclusion Q3G reduces the NTD rate in the embryos of diabetic dams. Q3G suppresses Nos2 and increases Sod1 expression, leading to alleviation of nitrosative, oxidative, and ER stress conditions. Q3G may regulate the expression of Nos2 via modulating the NF-κB transcription regulation system. Q3G, a naturally occurring polyphenol that has high bioavailability and low toxicity, is a promising candidate agent to prevent birth defects in diabetic pregnancies. Condensation The phytochemical quercetin-3-glucoside prevents neural tube defects in embryos of diabetic mice by alleviating nitrosative stress via suppression of the nuclear factor κB-regulated nitric oxide synthase 2 expression.

      PubDate: 2018-05-18T16:00:48Z
      DOI: 10.1016/j.ajog.2018.04.045
       
  • Abdominal skeletal muscle activity precedes spontaneous menstrual cramping
           pain in primary dysmenorrhea
    • Authors: Folabomi A. Oladosu; Frank. F. Tu; Saaniya Farhan; Ellen F. Garrison; Nicole D. Steiner; Genevieve E. Roth; Kevin M. Hellman
      Abstract: Publication date: Available online 5 May 2018
      Source:American Journal of Obstetrics and Gynecology
      Author(s): Folabomi A. Oladosu, Frank. F. Tu, Saaniya Farhan, Ellen F. Garrison, Nicole D. Steiner, Genevieve E. Roth, Kevin M. Hellman
      Background Dysmenorrhea is a pervasive pain condition that affects 20-50% of reproductive-aged women. Distension of a visceral organ, such as the uterus, could elicit a viscero-motor reflex resulting in involuntary skeletal muscle activity and referred pain. Although referred abdominal pain mechanisms can contribute to visceral pain, the role of abdominal muscle activity has not yet been investigated within the context of menstrual pain. Objective The goal of this study is to determine if involuntary abdominal muscle activity precedes spontaneous episodes of menstrual cramping pain in dysmenorrheic women and if naproxen administration affects abdominal muscle activity. Study Design Abdominal electromyography activity was recorded from women with severe dysmenorrheic (n=38) and healthy controls (n=10) during menses. Simultaneously, pain was measured in real-time using a squeeze-bulb or visual analog rheostat. Ninety minutes after naproxen administration, abdominal electromyography activity and menstrual pain were re-assessed. As an additional control, women were also recorded off-menses and data were analyzed in relation to random bulb squeezes. Since it is unknown whether mechanisms of menstrual cramps are different in primary or secondary dysmenorrhea/chronic pelvic pain, the relationship between medical history and abdominal muscle activity was examined. To further examine differences in nociceptive mechanisms, pressure pain thresholds were also measured to evaluate changes in widespread pain sensitivity. Results Abdominal muscle activity related to random-bulb squeezing was rarely observed in healthy controls on menses (0.9 ±0.6 episodes / hour) and in dysmenorrhea participants off menses (2.3 ± 0.6 episodes / hour). In dysmenorrheic participants during menses, abdominal muscle activity was frequently associated with bulb-squeezing indicative of menstrual cramping pain (10.8 ± 3.0 episodes / hour; p <0.004). Whereas 45% (17/38) of the women with dysmenorrhea had episodes of abdominal muscle activity associated pain, only 13% (5/38) had episodes after naproxen (p = 0.011). Women with the abdominal muscle activity-associated pain were less likely to have a diagnosis for secondary dysmenorrhea or chronic pelvic pain (2/17) than women without this pain phenotype (10/21; p = 0.034). Similarly, women with the abdominal muscle activity-associated pain phenotype had less non-menstrual pain days/month (0.6 ± 0.5) than women without the phenotype (12.4 ± 0.3; p = 0.002). Women with abdominal muscle activity-associated pain had pressure pain thresholds (22.4 ± 3.0 N) comparable to healthy controls (22.2 ± 3.0 N; p = 0.967). In contrast, women without abdominal muscle activity-associated pain had lower pressure pain thresholds (16.1 ± 1.9 N; p = 0.039). Conclusions Abdominal muscle activity may contribute to cramping pain in primary dysmenorrhea, but is resolvable with naproxen. Dysmenorrheic patients without cramp-associated abdominal muscle activity exhibit widespread pain sensitivity (lower pressure pain thresholds) and are more likely to also have a chronic pain diagnosis, suggesting their cramps are linked to changes in central pain processes. This preliminary study suggests new tools to phenotype menstrual pain and supports the hypothesis that multiple distinct mechanisms may contribute to dysmenorrhea.

      PubDate: 2018-05-18T16:00:48Z
      DOI: 10.1016/j.ajog.2018.04.050
       
  • The Vaginal Eukaryotic DNA Virome and Preterm Birth
    • Authors: Kristine M. Wylie; Todd N. Wylie; Alison G. Cahill; George A. Macones; Methodius G. Tuuli; Molly J. Stout
      Abstract: Publication date: Available online 5 May 2018
      Source:American Journal of Obstetrics and Gynecology
      Author(s): Kristine M. Wylie, Todd N. Wylie, Alison G. Cahill, George A. Macones, Methodius G. Tuuli, Molly J. Stout
      Background Despite decades of attempts to link infectious agents to preterm birth, an exact causative microbe or community of microbes remains elusive. Culture-independent sequencing of vaginal bacterial communities demonstrates community characteristics are associated with preterm birth, although none are specific enough to apply clinically. Viruses are important components of the vaginal microbiome and have dynamic relationships with vaginal bacterial communities. We hypothesized that vaginal eukaryotic DNA viral communities (the “vaginal virome”) either alone or in the context of bacterial communities are associated with preterm birth. Objective The objective of this study was to use high-throughput sequencing to examine the vaginal eukaryotic DNA virome in a cohort of pregnant women and examine associations between vaginal community characteristics and preterm birth. Study Design This is a nested case-control study within a prospective cohort study of women with singleton pregnancies, not on supplemental progesterone, and without cervical cerclage in situ. Serial mid-vaginal swabs were obtained at routine prenatal visits. DNA was extracted, bacterial communities were characterized by 16S rRNA gene sequencing, and eukaryotic viral communities were characterized by enrichment of viral nucleic acid with the ViroCap targeted sequence capture panel followed by nucleic acid sequencing. Viral communities were analyzed according to presence/absence of viruses, diversity, dynamics over time, and association with bacterial community data obtained from the same specimens. Results Sixty subjects contributed 128 vaginal swabs longitudinally across pregnancy. Twenty-four patients delivered preterm. Participants were predominantly African-American (65%). Six families of eukaryotic DNA viruses were detected in the vaginal samples. At least 1 virus was detected in 80% of women. No specific virus or group of viruses was associated with preterm delivery. Higher viral richness was significantly associated with preterm delivery in the full group and in the African American subgroup (P=0.0005 and P=0.0003, respectively). Having both high bacterial diversity and high viral diversity in the first trimester was associated with the highest risk for preterm birth. Conclusions Higher vaginal viral diversity is associated with preterm birth. Changes in vaginal virome diversity appear similar to changes in the vaginal bacterial microbiome over pregnancy, suggesting that underlying physiology of pregnancy may regulate both bacterial and viral communities.

      PubDate: 2018-05-18T16:00:48Z
      DOI: 10.1016/j.ajog.2018.04.048
       
  • Clinical Opinion: “Doing Something” About the Cesarean
           Delivery Rate
    • Authors: S.L. Clark; T.J. Garite; E.J. Hamilton; M.A. Belfort; G.D. Hankins
      Abstract: Publication date: Available online 5 May 2018
      Source:American Journal of Obstetrics and Gynecology
      Author(s): S.L. Clark, T.J. Garite, E.J. Hamilton, M.A. Belfort, G.D. Hankins
      There is a general consensus that the cesarean delivery rate in the U.S. is too high, and that practice patterns of obstetricians are largely to blame for this situation. In reality, the U.S. cesarean delivery rate is the result of 3 forces largely beyond the control of the practicing clinician: patient expectations and misconceptions regarding the safety of labor, the medical-legal system, and limitations in technology. Efforts to “do something” about the cesarean delivery rate by promulgating practice directives which are marginally evidence-based or influenced by social pressures are both ineffective and potentially harmful. We examine both the recent ACOG/SMFM Care Consensus Statement “Safe Prevention of Primary Cesarean Delivery” document and the various iterations of the ACOG guidelines for vaginal birth after cesarean delivery in this context. Adherence to arbitrary time limits for active phase or second stage arrest without incorporating other clinical factors into the decision making process is unwise. In a similar manner, ever-changing practice standards for vaginal birth after cesarean driven by factors other than changing data are unlikely to be effective in lowering the cesarean delivery rate. Whether too high or too low, the current U.S. cesarean delivery rate is the expected result of the unique demographic, geographic and social forces driving it and is unlikely to change significantly given the limitations of current technology to otherwise satisfy the demands of these forces.

      PubDate: 2018-05-18T16:00:48Z
      DOI: 10.1016/j.ajog.2018.04.044
       
  • Viewpoint: Barriers to Insurance Coverage for Transgender Patients
    • Authors: Claire Learmonth; Rebekah Viloria; Cei Lambert; Hilary Goldhammer; Alex Keuroghlian
      Abstract: Publication date: Available online 5 May 2018
      Source:American Journal of Obstetrics and Gynecology
      Author(s): Claire Learmonth, Rebekah Viloria, Cei Lambert, Hilary Goldhammer, Alex Keuroghlian
      Transgender people report discrimination in access to health care that is associated with numerous poor health outcomes, including higher prevalence of HIV infection, substance use disorders, and suicide attempts. The field of obstetrics and gynecology (OBGYN) is uniquely positioned to meet a wide range of health care needs for transgender people, and OGBYN clinicians can and ought to provide gender-affirming care for these patients. Despite growing evidence that gender-affirming care is both necessary and cost-effective, transgender patients continue to face barriers to securing insurance coverage, which prevents clinicians from practicing standards of care. The purpose of this article is to delineate the major barriers transgender patients face when seeking insurance reimbursement for services routinely available to cisgender (non-transgender) women.

      PubDate: 2018-05-18T16:00:48Z
      DOI: 10.1016/j.ajog.2018.04.046
       
  • Placenta percreta is associated with more frequent severe maternal
           morbidity than placenta accreta
    • Authors: Louis Marcellin; Pierre Delorme; Marie Pierre Bonnet; Gilles Grange; Gilles Kayem; Vassilis Tsatsaris; François Goffinet
      Abstract: Publication date: Available online 5 May 2018
      Source:American Journal of Obstetrics and Gynecology
      Author(s): Louis Marcellin, Pierre Delorme, Marie Pierre Bonnet, Gilles Grange, Gilles Kayem, Vassilis Tsatsaris, François Goffinet
      Background Abnormally invasive placentation is the leading cause of obstetric hysterectomy and can cause poor to disastrous maternal outcomes. Most previous studies of peripartum management and maternal morbidity have included variable proportions of severe and less severe cases. Objective The aim of this study was to compare maternal morbidity from placenta percreta and accreta. Study design This retrospective study at a referral center in Paris includes all women with abnormally invasive placentation from 2003 to 2017. Placenta percreta and accreta were diagnosed histologically or clinically. When placenta percreta was suspected before birth, a conservative approach leaving the placenta in situ was proposed because of the intraoperative risk of cesarean delivery. When placenta accreta was suspected, parents were offered a choice of a conservative approach or an attempt to remove the placenta, to be followed in case of failure by hysterectomy. Maternal outcomes were compared between women with placenta percreta and those with placenta accreta/increta. The primary outcome measure was a composite criterion of severe acute maternal morbidity including at least one of the following: hysterectomy during cesarean delivery, delayed hysterectomy, transfusion of ≥ 10 units of packed red blood cells, septic shock, acute kidney injury, cardiovascular failure, maternal transfer to intensive care, or death. Results Of the 156 women included, 51 had placenta percreta and 105 placenta accreta. Abnormally invasive placentation was suspected antenatally nearly four times more frequently in the percreta than the accreta group (96.1% (49/51) vs. 25.7% (27/105), P <0.01). Among the 76 women with antenatally suspected abnormally invasive placentation (48.7%), the rate of antenatal decisions for conservative management was higher in the percreta than the accreta group (100% (49/49) vs. 40.7% (11/27), P<0.01). The composite maternal morbidity rate was significantly higher in the percreta than the accreta group (86.3% (44/51) vs. 28/105 (26.7%), P <0.001). A secondary analysis restricted to women with an abnormally invasive placentation diameter > 6 cm showed similar results (86.0% (43/50) vs. 48.7% (19/38), P <0.01). The rate of hysterectomy during cesareans was significantly higher in the percreta than the accreta group (52.9% (27/51) vs. 20.9% (22/105), P < 0.01) as was the total hysterectomy rate (43/51 (84.3%) vs. 23.8% (25/105), P <0.01). Conclusion Severe maternal morbidity is much more frequent in women with placenta percreta than with placenta accreta, despite multidisciplinary planning, management in a referral center, and better antenatal suspicion.

      PubDate: 2018-05-18T16:00:48Z
      DOI: 10.1016/j.ajog.2018.04.049
       
  • Femur-Sparing Pattern of Abnormal Fetal Growth in Pregnant Women from New
           York City After Maternal Zika Virus Infection
    • Authors: Christie L. Walker; Audrey A. Merriam; Eric O. Ohuma; Manjiri K. Dighe; Michael Gale; Lakshmi Rajagopal; Aris T. Papageorghiou; Cynthia Gyamfi-Bannerman; Kristina M. Adams Waldorf
      Abstract: Publication date: Available online 5 May 2018
      Source:American Journal of Obstetrics and Gynecology
      Author(s): Christie L. Walker, Audrey A. Merriam, Eric O. Ohuma, Manjiri K. Dighe, Michael Gale, Lakshmi Rajagopal, Aris T. Papageorghiou, Cynthia Gyamfi-Bannerman, Kristina M. Adams Waldorf
      Background Zika virus (ZIKV) is a mosquito-transmitted flavivirus, which can induce fetal brain injury and growth restriction following maternal infection during pregnancy. Prenatal diagnosis of ZIKV-associated fetal injury in the absence of microcephaly is challenging due to an incomplete understanding of how maternal ZIKV infection affects fetal growth and the use of different sonographic reference standards around the world. We hypothesized that skeletal growth is unaffected by ZIKV infection and that the femur length can represent an internal standard to detect growth deceleration of the fetal head and/or abdomen by ultrasound. Objective To determine if maternal ZIKV infection is associated with a femur-sparing pattern of intrauterine growth restriction (IUGR) through analysis of fetal biometric measures and/or body ratios using the INTERGROWTH-21st Project (IG-21) and World Health Organization Fetal Growth Chart (WHO-FGC) sonographic references. Study Design Pregnant women diagnosed with a possible recent ZIKV infection at Columbia University Medical Center after traveling to an endemic area were retrospectively identified and included if a fetal ultrasound was performed. Data was collected regarding ZIKV testing, fetal biometry, pregnancy and neonatal outcomes. The IG-21 and WHO-FGC sonographic standards were applied to obtain Z-scores and/or percentiles for fetal head, abdominal circumference (HC, AC) and femur length (FL) specific for each gestational week. A novel IG-21 standard was also developed to generate Z-scores for fetal body ratios with respect to femur length (HC:FL, AC:FL). Data was then grouped within clinically relevant gestational age strata (<24 weeks, 24-27 6/7, 28-33 6/7, >34 weeks) to analyze time-dependent effects of ZIKV infection on fetal size. Statistical analysis was performed using Wilcoxon signed-rank test on paired data, comparing either AC or HC to FL. Results A total of 56 pregnant women were included in the study with laboratory evidence of a confirmed or possible recent ZIKV infection. Based on the CDC definition for microcephaly after congenital ZIKV exposure, microcephaly was diagnosed in 5% (3/56) by both the IG-21 and WHO-FGC standards (HC Z-score ≤ -2 or ≤ 2.3%). Using IG-21, IUGR was diagnosed in 18% of pregnancies (10/56; AC Z-score ≤-1.3, <10%). Analysis of fetal size using the last ultrasound scan for all subjects revealed a significantly abnormal skewing of fetal biometrics with a smaller AC versus FL by either IG-21 or WHO-FGC (p<0.001 for both). A difference in distribution of fetal AC compared to FL was first apparent in the 24-27 6/7 week strata (IG-21, p=0.002; WHO-FGC, p=0.001). A significantly smaller HC compared to FL was also observed by IG-21 as early as the 28-33 6/7 week strata (IG-21, p=0.007). Overall, a femur-sparing pattern of growth restriction was detected in 52% of pregnancies with either an HC:FL or AC:FL fetal body ratio less than the 10th percentile (IG-21 Z-score ≤-1.3). Conclusions An unusual femur-sparing pattern of fetal growth restriction was detected in the majority of fetuses with congenital ZIKV exposure. Fetal body ratios may represent a more sensitive ultrasound biomarker to detect viral injury in nonmicrocephalic fetuses that could impart long-term risk for complications of congenital ZIKV infection.

      PubDate: 2018-05-18T16:00:48Z
      DOI: 10.1016/j.ajog.2018.04.047
       
  • Information for Readers
    • Abstract: Publication date: May 2018
      Source:American Journal of Obstetrics and Gynecology, Volume 218, Issue 5


      PubDate: 2018-05-01T14:44:16Z
       
  • Lessons learned from domestic and international human papillomavirus
           vaccination programs: a review
    • Authors: Kathryn Miller; Sarah Dilley Warner Huh
      Abstract: Publication date: May 2018
      Source:American Journal of Obstetrics and Gynecology, Volume 218, Issue 5
      Author(s): Kathryn Miller, Sarah E. Dilley, Warner K. Huh
      Since the development of the human papillomavirus vaccine, many countries have created implementation programs to bolster vaccination rates and protect their populations. Despite demonstrated efficacy with decreased human papillomavirus–related disease abroad, the vaccine's potential to prevent morbidity and mortality in the United States is not being met. The purpose of this review is to discuss strategies of both international and domestic vaccination programs, their impact on human papillomavirus–related diseases, the unique obstacles faced by the United States, and future directions for success.

      PubDate: 2018-05-01T14:44:16Z
       
  • Cine MRI during spontaneous cramps in women with menstrual pain
    • Authors: Kevin Hellman; Caroline Kuhn Frank Katlyn Dillane Nathan Shlobin Sangeeta
      Abstract: Publication date: May 2018
      Source:American Journal of Obstetrics and Gynecology, Volume 218, Issue 5
      Author(s): Kevin M. Hellman, Caroline S. Kuhn, Frank F. Tu, Katlyn E. Dillane, Nathan A. Shlobin, Sangeeta Senapati, Xiaojie Zhou, Wei Li, Pottumarthi V. Prasad
      Background The lack of noninvasive methods to study dysmenorrhea has resulted in poor understanding of the mechanisms underlying pain, insufficient diagnostic tests, and limited treatment options. To address this knowledge gap, we have developed a magnetic resonance imaging–based strategy for continuously monitoring the uterus in relationship to participants’ spontaneous pain perception. Objective The study objective was to evaluate whether magnetic resonance imaging can detect real-time changes in myometrial activity during cramping episodes in women with dysmenorrhea, with a handheld squeeze bulb for pain reporting. Study Design Sixteen women with dysmenorrhea and 10 healthy control women both on and off their menses were evaluated with magnetic resonance imaging while not taking analgesic medication. Continuous magnetic resonance imaging was acquired using half-Fourier acquisition single-shot turbo spin echo sequence along with simultaneous reporting of pain severity with a squeeze bulb. Pearson’s coefficient was used to compare results between reviewers. Proportional differences between women with dysmenorrhea and controls on/off menses were evaluated with a Fisher exact test. The temporal relationships between signal changes were evaluated with Monte Carlo simulations. Results Spontaneous progressive decreases in myometrial signal intensity were more frequently observed in women on their menses than in the absence of pain in the same women off their menses or participants without dysmenorrhea (P < .01). Women without reductions in myometrial signal intensity on their menses either had a history of endometriosis or were not in pain. Observations of myometrial events were consistently reported between 2 raters blinded to menstrual pain or day status (r = 0.97, P < .001). Episodes of cramping occurred either immediately before or 32–70 seconds after myometrial signal change onset (P < .05). Conclusion Transient decreases in myometrial uterine T2-weighted signal intensity can be reliably measured in women with menstrual pain. The directionality of signal change and temporal relationship to pain onset suggest that cramping pain may be caused by a combination of uterine pressure and hemodynamic dysfunction.

      PubDate: 2018-05-01T14:44:16Z
       
  • October 2017 (vol. 217, no. 4, page B22)
    • Abstract: Publication date: May 2018
      Source:American Journal of Obstetrics and Gynecology, Volume 218, Issue 5


      PubDate: 2018-05-01T14:44:16Z
       
  • December 2017 (vol. 217, no. 6, page 682)
    • Abstract: Publication date: May 2018
      Source:American Journal of Obstetrics and Gynecology, Volume 218, Issue 5


      PubDate: 2018-05-01T14:44:16Z
       
 
 
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