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BACKGROUND: Preterm birth is a global health priority. Using a progestogen during high-risk pregnancy could reduce preterm birth and adverse neonatal outcomes.METHODS: We did a systematic review of randomised trials comparing vaginal progesterone, intramuscular 17-hydroxyprogesterone caproate (17-OHPC), or oral progesterone with control, or with each other, in asymptomatic women at risk of preterm birth. We identified published and unpublished trials that completed primary data collection before July 30, 2016, (12 months before data collection began), by searching MEDLINE, Embase, CINAHL, the Maternity and Infant Care Database, and relevant trial registers between inception and July 30, 2019. Trials of progestogen to prevent early miscarriage or immediately-threatened preterm birth were excluded. Individual participant data were requested from investigators of eligible trials. Outcomes included preterm birth, early preterm birth, and mid-trimester birth. Adverse neonatal sequelae associated with early births were assessed using a composite of serious neonatal complications, and individually. Adverse maternal outcomes were investigated as a composite and individually. Individual participant data were checked and risk of bias assessed independently by two researchers. Primary meta-analyses used one-stage generalised linear mixed models that incorporated random effects to allow for heterogeneity across trials. This meta-analysis is registered with PROSPERO, CRD42017068299.FINDINGS: Initial searches identified 47 eligible trials. Individual participant data were available for 30 of these trials. An additional trial was later included in a targeted update. Data were therefore available from a total of 31 trials (11 644 women and 16185 offspring). Trials in singleton pregnancies included mostly women with previous spontaneous preterm birth or short cervix. Preterm birth before 34 weeks was reduced in such women who received vaginal progesterone (nine trials, 3769 women; relative risk [RR] 0·78, 95% CI 0·68-0·90), 17-OHPC (five trials, 3053 women; 0·83, 0·68-1·01), and oral progesterone (two trials, 181 women; 0·60, 0·40-0·90). Results for other birth and neonatal outcomes were consistently favourable, but less certain. A possible increase in maternal complications was suggested, but this was uncertain. We identified no consistent evidence of treatment interaction with any participant characteristics examined, although analyses within subpopulations questioned efficacy in women who did not have a short cervix. Trials in multifetal pregnancies mostly included women without additional risk factors. For twins, vaginal progesterone did not reduce preterm birth before 34 weeks (eight trials, 2046 women: RR 1·01, 95% CI 0·84-1·20) nor did 17-OHPC for twins or triplets (eight trials, 2253 women: 1·04, 0·92-1·18). Preterm premature rupture of membranes was increased with 17-OHPC exposure in multifetal gestations (rupture INTERPRETATION: Vaginal progesterone and 17-OHPC both reduced birth before 34 weeks' gestation in high-risk singleton pregnancies. Given increased underlying risk, absolute risk reduction is greater for women with a short cervix, hence treatment might be most useful for these women. Evidence for oral progesterone is insufficient to support its use. Shared decision making with woman with high-risk singleton pregnancies should discuss an individual's risk, potential benefits, harms and practicalities of intervention. Treatment of unselected multifetal pregnancies with a progestogen is not supported by the evidence.FUNDING: Patient-Centered Outcomes Research Institute.

New findings What is the central question of this study? Is chemerin, an adipokine implicated in obesity, increased in neonates following in utero cigarette smoke exposure. What is the main finding and its importance? Chemerin mRNA expression was increased and chemerin DNA methylation was decreased in babies born to mothers who smoked during pregnancy. These data provide a potential mechanism that may be mediating the increased obesity risk in individuals that are born to mothers who smoked during pregnancy. Abstract It has been shown that in utero tobacco exposure increases offspring risk for obesity, but the mechanisms responsible for this increased risk are not well understood. Chemerin is an adipokine that regulates adipocyte differentiation. This chemokine is elevated in obese individuals and with smoke exposure, but its levels have not been measured in neonates exposed to cigarette smoke in utero. We examined chemerin gene expression [n = 31 non-smoker (NS) and 15 smoker (S)] and DNA methylation (n = 28 NS and n = 11 S) in skin collected from babies born to mothers who smoked during pregnancy as compared to non-smoking controls. Quality RNA and DNA were isolated from foreskin tissue following circumcision, and chemerin gene expression and DNA methylation were assessed. Further, in a second cohort, we utilized primary dermal foreskin fibroblasts as a functional measure of adipogenesis in living cells (n = 11 NS and n = 8 S). Cells were stimulated with an adipogenic cocktail, mRNA was isolated from cells after 14 days, and chemerin gene expression assessed via real-time PCR. Chemerin mRNA was elevated in both whole tissue (NS: 2409.20 ± 555.28 counts and S: 2966.72 ± 636.84 counts; P 0.55 2 Δ Δ C T and S: 2.13 ± 1.34 2 Δ Δ C T ; P = 0.04) collected from infants born to smoking mothers. Chemerin DNA methylation was reduced in whole tissue of offspring born to smokers (NS: 4.18 ± 1.28 and S: 3.07 ± 1.31%; P = 0.02), which may contribute to the increased gene expression. Neonates born to mothers who smoke during pregnancy exhibit distinct changes in chemerin gene expression in response to in utero tobacco smoke exposure which are regulated in part by epigenetic alterations.

Reducing the risk of developing chronic disease, such as obesity and type 2 diabetes, is an important component of successful aging. Offspring born to mothers who exercise during pregnancy have improved body composition and metabolic profiles. However, mechanisms to explain this phenomenon are lacking.PurposeThis study examined whether maternal step counts were correlated with neonatal gene expression markers related to glucose metabolism and adipogenesis.MethodsPhysical activity levels were assessed in women with male neonates via Fitbit Flex® during the second and third trimester of pregnancy. The dartos and epidermal/dermal layers of the foreskin were collected following circumcision in full-term, singleton, neonates (n = 12 dartos and n = 14 dermal). Tissue was homogenized, RNA isolated, and a NanoString code set was run to quantify a panel of genes related to glucose metabolism and adipogenesis.ResultsTwelve genes were correlated to steps per day with a P-value of P-value < 0.10). Notably, glucose transporter 1, adiponectin receptor 1, and CCAAT/enhancer-binding protein alpha and beta were positively correlated with steps per day, while peroxisome proliferator-activated receptor alpha and peroxisome proliferator-activated receptor gamma coactivator 1- alpha were negatively correlated with steps per day.ConclusionMaternal physical activity is associated with offspring gene expression markers of adipogenesis, insulin sensitivity and glucose uptake. Future studies should aim to mechanistically examine whether these markers are driving increased adiposity in offspring born to sedentary mothers.

BackgroundAn indirect comparison meta-analysis published in 2013 reported that both vaginal progesterone and cerclage are equally efficacious for preventing preterm birth and adverse perinatal outcomes in women with a singleton gestation, previous spontaneous preterm birth and a sonographic short cervix. The efficacy of vaginal progesterone has been disputed after publication of the OPPTIMUM study.ObjectiveTo compare the efficacy of vaginal progesterone and cerclage in preventing preterm birth and adverse perinatal outcomes in women with a singleton gestation, previous spontaneous preterm birth and a midtrimester sonographic short cervix.Data SourcesMEDLINE, EMBASE, LILACS, and CINAHL (from their inception to March 2018); Cochrane databases, bibliographies, and conference proceedings.Study Eligibility CriteriaRandomized controlled trials comparing vaginal progesterone with placebo/no treatment or cerclage with no cerclage in women with a singleton gestation, previous spontaneous preterm birth and a sonographic cervical length Study Appraisal and Synthesis MethodsUpdated systematic review and adjusted indirect comparison meta-analysis of vaginal progesterone versus cerclage using placebo/no cerclage as the common comparator. The primary outcomes were preterm birth ResultsFive trials comparing vaginal progesterone versus placebo (265 women) and 5 comparing cerclage versus no cerclage (504 women) were included. Vaginal progesterone, compared with placebo, significantly reduced the risk of preterm birth ConclusionsVaginal progesterone and cerclage are equally effective for preventing preterm birth and improving perinatal outcomes in women with a singleton gestation, previous spontaneous preterm birth, and a midtrimester sonographic short cervix. The choice of treatment will depend on adverse events and cost-effectiveness of interventions, and patient/physician’s preferences.

Objective To assess differences in cytokine levels in cervicovaginal fluid (CVF) and serum across trimesters between women with preterm births (PTBs) and full-term births. Study Design This multicenter study enrolled 302 women with a singleton gestation. CVF and serum cytokines, interleukin 1α (IL-1α), IL-1β, IL-6, IL-8, IL-10, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, and matrix metalloproteinase (MMP)-8, were measured. Women with at least one cytokine assessment and noted PTB status in their medical record were retained in the study (N = 272). Data were analyzed using mixed modeling (main effects of PTBs and time/trimester). Results For the CVF values of IL-6, IL-8, IL-10, TNF-α, and CRP, and serum MMP-8, those who delivered preterm had significantly higher values than the full-term group regardless of trimester. For the serum values of IL-1β, IL-6, and TNF-α, those delivering preterm had significantly lower values than those delivering full-term regardless of trimester. For IL-1β in CVF, the cytokine was significantly higher in the PTB group for second and third trimesters only, relative to the full-term group. Conclusion For each CVF cytokine that differed by birth status, values were higher for PTB than term, averaged over trimester. Numerous cytokine profiles varied across trimesters in women delivering term versus preterm in both CVF and serum.

Background The efficacy of vaginal progesterone for preventing preterm birth and adverse perinatal outcomes in singleton gestations with a short cervix has been questioned after publication of the OPPTIMUM study. Objective To determine whether vaginal progesterone prevents preterm birth and improves perinatal outcomes in asymptomatic women with a singleton gestation and a midtrimester sonographic short cervix. Study Design We searched MEDLINE, EMBASE, LILACS, and CINAHL (from their inception to September 2017); Cochrane databases; bibliographies; and conference proceedings for randomized controlled trials comparing vaginal progesterone vs placebo/no treatment in women with a singleton gestation and a midtrimester sonographic cervical length ≤25 mm. This was a systematic review and meta-analysis of individual patient data. The primary outcome was preterm birth Results Data were available from 974 women (498 allocated to vaginal progesterone, 476 allocated to placebo) with a cervical length ≤25 mm participating in 5 high-quality trials. Vaginal progesterone was associated with a significant reduction in the risk of preterm birth Conclusion Vaginal progesterone decreases the risk of preterm birth and improves perinatal outcomes in singleton gestations with a midtrimester sonographic short cervix, without any demonstrable deleterious effects on childhood neurodevelopment.

Objective This study describes the normal variations in serum and cervicovaginal fluid (CVF) cytokine levels throughout pregnancy. Study Design This multicenter, prospective study examined trimester-specific maternal serum and CVF cytokines (interleukin [IL]-1α, IL-1β, IL-6, IL-8, IL-10, tumor necrosis factor-α, and C-reactive protein [CRP]). A two-factor linear mixed modeling approach compared cytokine distribution, while pairwise comparisons evaluated differences over time. Results Trimester-specific serum cytokine data were available for 288, 243, and 221 patients, whereas CVF cytokine data were available for 273, 229, and 198 patients. CVF had significantly higher concentrations of IL-1α, IL-1β, IL-6, IL-8, and matrix metalloproteinase-8 (p Conclusion Differences in cytokine distribution across different biological fluids are evident throughout pregnancy. These findings provide a framework for examining patterns of changes in cytokines throughout pregnancy.

Elevated birth weight is linked to glucose intolerance and obesity health-related complications later in life. No studies have examined if infant birth weight is associated with gene expression markers of obesity and inflammation in a tissue that comes directly from the infant following birth. We evaluated the association between birth weight and gene expression on fetal programming of obesity. Foreskin samples were collected following circumcision, and gene expression analyzed comparing the 15% greatest birth weight infants (n=7)v.the remainder of the cohort (n=40). Multivariate linear regression models were fit to relate expression levels on differentially expressed genes to birth weight group with adjustment for variables selected from a list of maternal and infant characteristics. Glucose transporter type 4 (GLUT4), insulin receptor substrate 2 (IRS2), leptin receptor (LEPR), lipoprotein lipase (LPL), low-density lipoprotein receptor-related protein 1 (LRP1), matrix metalloproteinase 2 (MMP2), plasminogen activator inhibitor-1 (PAI-1) and transcription factor 7-like 2 (TCF7L2) were significantly upregulated and histone deacetylase 1 (HDAC1) and thioredoxin (TXN) downregulated in the larger birth weight neonatesv. controls. Multivariate modeling revealed that the estimated adjusted birth weight group difference exceeded one standard deviation of the expression level for eight of the 10 genes. Between 25 and 50% of variation in expression level was explained by multivariate modeling for eight of the 10 genes. Gene expression related to glycemic control, appetite/energy balance, obesity and inflammation were altered in tissue from babies with elevated birth weight, and these genes may provide important information regarding fetal programming in macrosomic babies.

Objective To evaluate the efficacy of vaginal progesterone administration for preventing preterm birth and perinatal morbidity and mortality in asymptomatic women with a singleton gestation and a mid‐trimester sonographic cervical length (CL) ≤ 25 mm. Methods This was an updated systematic review and meta‐analysis of randomized controlled trials comparing the use of vaginal progesterone to placebo/no treatment in women with a singleton gestation and a mid‐trimester sonographic CL ≤ 25 mm. Electronic databases, from their inception to May 2016, bibliographies and conference proceedings were searched. The primary outcome measure was preterm birth ≤ 34 weeks of gestation or fetal death. Two reviewers independently selected studies, assessed the risk of bias and extracted the data. Pooled relative risks (RRs) with 95% confidence intervals (CI) were calculated. Results Five trials involving 974 women were included. A meta‐analysis, including data from the OPPTIMUM study, showed that vaginal progesterone significantly decreased the risk of preterm birth ≤ 34 weeks of gestation or fetal death compared to placebo (18.1% vs 27.5%; RR, 0.66 (95% CI, 0.52–0.83); P = 0.0005; five studies; 974 women). Meta‐analyses of data from four trials (723 women) showed that vaginal progesterone administration was associated with a statistically significant reduction in the risk of preterm birth occurring at, This article has been selected for Journal Club. Click here to view slides and discussion points.

Objective To evaluate the association of biochemically validated prenatal tobacco use with serum progesterone and estradiol in the second trimester of pregnancy, controlling for demographic and personal factors. Study design This secondary analysis of a multicenter longitudinal study included 114 women with singleton pregnancies. Multiple regression analysis assessed whether prenatal tobacco use was related to hormone levels during the second trimester, controlling for covariates (age, body mass index, and race or ethnicity, with gestational age added to subsequent models). Result In the initial regressions, tobacco users had significantly lower progesterone level compared with nonsmokers ( p = .037), while estradiol was unrelated to prenatal tobacco use. Women with greater body mass index also had significantly lower progesterone ( p = .028), but body mass index was unrelated to estradiol. With gestational age as an additional covariate, prenatal tobacco use was no longer a significant predictor of progesterone, but both body mass index and gestational age were significant ( F = 10.6, p 2 = 0.35). For estradiol, the overall regression of estradiol on age, body mass index, and race or ethnicity was not significant ( F = 1.2, p = .31). With gestational age added to the model, the overall model was significant ( F = 7.2, p 2 = 0.27). Conclusion This study provides additional evidence that prenatal tobacco use may influence lower serum progesterone during the second trimester. This is of particular concern given the link between depressed progesterone activity and risk for preterm birth.

The complex interactions between genes and the environment yield multiple pathophysiologies for the great obstetrical diseases such as preterm birth (Romero R et al, Science, 2014, 345,760-765). Our current, limited capacity to define when and to what extent any number of these pathophysiologies are in effect in individual pregnant patients has resulted in therapeutic strategies being aimed preferentially toward populations defined by risk factors, particularly obstetrical history. However, strategies such as prophylactic progestogen administration indicated for a prior preterm birth necessarily overtreat pregnant women exposing them and their children to potential, possibly unforeseen, harm (O'Brien JM, BJOG 2015;122:610-614). This article is protected by copyright. All rights reserved.

Objective We hypothesized that, as has been shown outside of pregnancy, endothelial dysfunction would be seen in a dose-dependent fashion among women who smoke in the midtrimester of pregnancy. Study Design Endothelial function in women with singleton pregnancies between 16 and 23 weeks was analyzed utilizing the Endo-PAT2000 device (Itamar Medical Ltd., Caesarea, Israel) and expressed as a reactive hyperemia ratio (RHI). Serum was drawn to check cotinine and high-sensitivity C-reactive protein (CRP) levels. SAS 9.2 (SAS Institute, Cary, NC) was used to perform statistical tests including Student t test, analysis of variance, Fisher exact test, and Pearson coefficient. Results Endothelial function was noninvasively examined in 29 smokers and 31 nonsmokers. Demographics including age, race, and parity were similar between groups. Mean RHI was not significantly different between smokers and nonsmokers (1.43 ± 0.32 versus 1.53 ± 0.39, p = 0.27). No correlation was noted when cotinine values were plotted against RHI or CRP values in smokers (rho = 0.24, p = 0.21 and rho = 0.26, p = 0.18, respectively). RHI did correlate with diastolic blood pressure (rho = −0.40, p = 0.002), systolic blood pressure (rho = −0.35, p = 0.006), and heart rate (rho = −0.37, p = 0.004). Conclusion We did not find an association between smoking status and endothelial dysfunction in the midtrimester utilizing a noninvasive methodology.

Background The likelihood of cesarean is in part related to maternal body mass index (BMI). Myometrial changes may be responsible. Methods Myometrial biopsies were collected from the upper edge of the hysterotomy from women undergoing scheduled cesarean with term, singleton gestations. Oxytocin receptor and connexin-43 mRNA protein expression was quantified with real-time polymerase chain reaction and Western blot. Results Twenty subjects were recruited: 13 repeat and 7 primary cesareans. Oxytocin receptor mRNA was associated with BMI among women undergoing primary ( r = 0.75; p = 0.05) but not repeat cesarean ( p > 0.05). Controlling for gestational age, this association strengthened ( p = 0.004). Receptor protein expression showed a linear correlation with BMI in the primary cesarean group ( p = 0.002). Connexin-43 mRNA expression was not related to BMI in women undergoing primary ( r = −0.14, p = 0.76) or repeat ( r = −0.01, p = 0.86) cesarean. Conclusions Oxytocin receptor, but not connexin-43, expression is related to BMI, suggesting an alteration in oxytocin receptor expression or function related to obesity.

The safety of supplemental progestin therapy during pregnancy reflects whether an agent exclusively promotes or potentially inhibits progestational cellular functions and whether treatment incites a metabolic derangement or other pathophysiology to initiate rare untoward events. No safety signal has been identified from intravaginal administration of natural progesterone from phase III clinical trials. The Food and Drug Administration has identified a legitimate safety signal regarding second-trimester miscarriage and stillbirth with exposure to 17-hydroxyprogesterone caproate (17-OHPC). Results from recent phase II and III trials in multiples also demonstrates concern with exposure to this synthetic for fetal loss and increased severe respiratory distress in neonates (one study each), as well as repeated significant associations for shorter duration of pregnancy and poorer fetal growth in others. The biological plausibility for 17-OHPC to be associated with adverse outcomes can be suggested from pharmacogenomic observations, ex vivo experimentation, and clinical observations. Further data are needed interrogating the potential for rare fetal or maternal adverse events/safety outcomes with exposure to progestins. Safety concerns should be incorporated into prescribing decisions.

Women with a sonographic short cervix in the mid-trimester are at increased risk for preterm delivery. This study was undertaken to determine the efficacy and safety of using micronized vaginal progesterone gel to reduce the risk of preterm birth and associated neonatal complications in women with a sonographic short cervix.This was a multicenter, randomized, double-blind, placebo-controlled trial that enrolled asymptomatic women with a singleton pregnancy and a sonographic short cervix (10-20 mm) at 19 + 0 to 23 + 6 weeks of gestation. Women were allocated randomly to receive vaginal progesterone gel or placebo daily starting from 20 to 23 + 6 weeks until 36 + 6 weeks, rupture of membranes or delivery, whichever occurred first. Randomization sequence was stratified by center and history of a previous preterm birth. The primary endpoint was preterm birth before 33 weeks of gestation. Analysis was by intention to treat.Of 465 women randomized, seven were lost to follow-up and 458 (vaginal progesterone gel, n=235; placebo, n=223) were included in the analysis. Women allocated to receive vaginal progesterone had a lower rate of preterm birth before 33 weeks than did those allocated to placebo (8.9% (n=21) vs 16.1% (n=36); relative risk (RR), 0.55; 95% CI, 0.33-0.92; P=0.02). The effect remained significant after adjustment for covariables (adjusted RR, 0.52; 95% CI, 0.31-0.91; P=0.02). Vaginal progesterone was also associated with a significant reduction in the rate of preterm birth before 28 weeks (5.1% vs 10.3%; RR, 0.50; 95% CI, 0.25-0.97; P=0.04) and 35 weeks (14.5% vs 23.3%; RR, 0.62; 95% CI, 0.42-0.92; P=0.02), respiratory distress syndrome (3.0% vs 7.6%; RR, 0.39; 95% CI, 0.17-0.92; P=0.03), any neonatal morbidity or mortality event (7.7% vs 13.5%; RR, 0.57; 95% CI, 0.33-0.99; P=0.04) and birth weight1500 g (6.4% (15/234) vs 13.6% (30/220); RR, 0.47; 95% CI, 0.26-0.85; P=0.01). There were no differences in the incidence of treatment-related adverse events between the groups.The administration of vaginal progesterone gel to women with a sonographic short cervix in the mid-trimester is associated with a 45% reduction in the rate of preterm birth before 33 weeks of gestation and with improved neonatal outcome.

We sought to reduce long-term complications after cesarean delivery by improving myometrial healing. Eight sheep (three with twins) underwent cesarean delivery. Hysterotomy sites were repaired in equal parts by suture alone or suture with a juxtaposed graft (Cook Medical, Bloomington, IN). At 90 days postsurgery, scar characteristics and tensile strength testing were assessed. The mean hysterotomy closure time was on average 1 minute, 14 seconds longer for those undergoing graft placement ( P = 0.36). The mean scar thickness was 3.0 ± 0.4 mm for controls versus 3.8 ± 1.2 mm for the intervention group ( P = 0.047). Tensile strength testing did not demonstrate a significant difference between groups. Histological examination of the myometrial scar showed no significant differences in inflammatory reaction or endometrial inclusions; however, neoangiogenesis was significantly enhanced. Myometrial repair incorporating a graft increased scar thickness and neoangiogenesis. This methodology did not incite adenomyosis or enhance inflammation within the scar.

A growing body of literature indicates that eye movement desensitization and reprocessing (EMDR) can be useful in the treatment of addictions. When combined with traditional addictions treatment approaches, EMDR can enhance client stability, prevent relapse, and promote recovery. Clinical decision making about when and how to use EMDR techniques with clients who present with addictions is complicated. The purpose of this article is to explore the use of EMDR interventions with clients presenting various levels of awareness of their addiction as well as varied levels of motivation to change. The authors explore the Stages of Change and suggest appropriate pre-EMDR EMDR interventions at each stage.

Progestogens are the first drugs to demonstrate reproducibly a reduction in the rate of early preterm birth. The efficacy and safety of progestogens are related to individual pharmacologic properties of each drug within this class of medication and characteristics of the population that is treated. The synthetic 17-hydroxyprogesterone caproate and natural progesterone have been studied with the use of a prophylactic strategy in women with a history of preterm birth and in women with a multiple gestation. Evidence from a single large comparative efficacy trial suggests that vaginal natural progesterone is superior to 17-hydroxyprogesterone caproate as a prophylactic treatment in women with a history of mid-trimester preterm birth. Progestogen therapy is indicated for women with this highest risk profile based on evidence from 2 trials. A therapeutic approach based on the identification of a sonographic short cervix has been studied in several phase III trials. Independent phase III trials and an individual patient metaanalysis suggest that vaginal progesterone is efficacious and safe in women with a singleton and a short cervix. Two trials that tested 17-hydroxyprogesterone caproate in women with a short cervix showed no benefit. No consistent benefit for the prophylactic or therapeutic use of progestogens has been demonstrated in larger trials of women whose pregnancies were complicated by a multiple gestation (twins or triplets), preterm labor, or preterm rupture of membranes. Unfortunately, several large randomized trials in multiple gestations have identified harm related to 17-hydroxyprogesterone caproate exposure, and the synthetic drug is contraindicated in this population. The current body of evidence is evaluated by the Grading of Recommendations Assessment, Development, and Evaluation guidelines to derive the strength of recommendation in each of these populations. A large confirmatory trial that is testing 17-hydroxyprogesterone caproate exposure in women with a singleton pregnancy and a history of preterm birth is near completion. Additional study of the efficacy and safety of progestogens is suggested in well-selected populations based on the presence of biomarkers.

Eye movement desensitization and reprocessing (EMDR) is a therapy that has been demonstrated to be effective in the treatment of posttraumatic stress disorder (PTSD). A relatively small but growing body of literature indicates that EMDR may be an effective adjunctive treatment for substance abuse. This article reviews the various protocols that have been developed for that purpose, including protocols by Vogelmann-Sine et al., Omaha, Popky, and Hase. A case study that incorporates the use of some of these interventions is presented to illustrate successful EMDR treatment of a woman who had long-standing comorbid alcohol abuse and PTSD. Two-year follow-up after EMDR showed that the woman was successfully maintaining sobriety and that the PTSD continued in full remission. After a discussion of the important aspects of this case, the authors explore future directions for research.

Purpose: This paper reports a case study of 7 Critical Access Hospitals’ (CAH) and 1 rural referral hospital's successful collaboration to develop a shared formulary. Methods: Study methods included document reviews, interviews with key informants, and use of descriptive statistics. Findings: Through a systematic review and decision process, CAH formularies ranging in size from 667 to 1,351 items were compared, rationalized, and consolidated resulting in an 803-item shared formulary. While the individual CAHs were generally expected to list and stock the same 803 items in the shared formulary's pharmacy information system, they could individually determine the amount to be stocked for each item, as well as stock additional items not included on the shared formulary to reflect local provider preferences and services provided. Final stocked formulary items ranged from 592 to 786 items among the 7 CAHs. Major challenges and lessons learned in the course of developing a shared formulary related to: Meeting Logistics, Facilitator to Manage the Process, Organizing the Review Process, Management Support, Stakeholder Participation, Working Collaboratively, Decision-Making Process, Clarity of Charge, Meeting the Needs of Unique Services, Communicating with Providers, and Adjusting to a Shared Formulary. Conclusions: Collaborating in the development of a shared formulary allows for a greater range of decision-making expertise, shared workload, and an improved formulary. An organized and well-managed group decision-making process is essential to a successful collaboration.

Gestational hypertension (GHTN) and gestational diabetes mellitus (GDM) are both insulin resistance states. Perinatal outcome of GHTN or GDM alone are well established, but their combined effect on pregnancy outcome is underinvestigated. Our objective was to determine if pregnancies complicated by GHTN/GDM have higher rates of morbidity. We identified nulliparous women with singleton pregnancies delivering at 37 to 40 weeks of gestation from 1995 to 2004 from a database. Outcomes of pregnancies complicated by GHTN only, GDM only, or combined GHTN/GDM were compared with controls. Data analysis included the Mann-Whitney U test, the Kruskal-Wallis H test, and analysis of variance. Multivariate analysis was used to adjust for confounders. Of 14,880 patients, there were 11,349 controls, 2604 GHTN, 728 GDM, and 199 GHTN/GDM. After controlling for covariates, GHTN significantly increased cesarean section (C/S) rate (odd ratio [OR], 1.62; confidence interval [CI], 1.47 to 1.78), rates of admittance to the neonatal intensive care unit (NICU), and birth of large for gestational age (LGA) infants. GDM significantly increased C/S (OR, 1.42; CI 1.21 to 1.66), rates of NICU admission (OR, 1.32; CI, 1 to 1.75), birth of LGA (OR, 1.51; CI 1.14 to 1.98), and macrosomic infants (OR, 1.53; CI, 1.12 to 2.08). Rates of LGA infants (OR, 1.85; CI, 1.19 to 2.86) and C/S (OR, 2.03; CI, 1.52 to 2.71) were significantly increased with GHTN/GDM. We concluded that GHTN or GDM is associated with increased rates of adverse outcomes. Their coexistence further increases adverse perinatal outcomes.

Objective Preterm birth is the leading cause of perinatal morbidity and mortality worldwide. Treatment of preterm labor with tocolysis has not been successful in improving infant outcome. The administration of progesterone and related compounds has been proposed as a strategy to prevent preterm birth. The objective of this trial was to determine whether prophylactic administration of vaginal progesterone reduces the risk of preterm birth in women with a history of spontaneous preterm birth. Methods This randomized, double-blind, placebo- controlled, multinational trial enrolled and randomized 659 pregnant women with a history of spontaneous preterm birth. Between 18 + 0 and 22 + 6 weeks of gestation, patients were assigned randomly to once-daily treatment with either progesterone vaginal gel or placebo until either delivery, 37 weeks' gestation or development of preterm rupture of membranes. The primary outcome was preterm birth at ≤ 32 weeks of gestation. The trial was analyzed using an intent-to-treat strategy. Results Baseline characteristics were similar in the two treatment groups. Progesterone did not decrease the frequency of preterm birth at ≤ 32 weeks. There was no difference between the groups with respect to the mean gestational age at delivery, infant morbidity or mortality or other maternal or neonatal outcome measures. Adverse events during the course of treatment were similar for the two groups. Conclusion Prophylactic treatment with vaginal progesterone did not reduce the frequency of recurrent preterm birth (≤ 32 weeks) in women with a history of spontaneous preterm birth. The effect of progesterone administration in patients at high risk for preterm delivery as determined by methods other than history alone (e.g. sonographic cervical length) requires further investigation. Copyright © 2007 ISUOG. Published by John Wiley & Sons, Ltd.

OBJECTIVE To estimate the incidence and effect of pregnancy-related hypertensive conditions on multiple gestations. METHODS Women with 1-4 fetuses enrolled in an outpatient perinatal services program at 28 or more weeks of gestation were identified. Those without a prior diagnosis of hypertension at enrollment and who delivered at more than 28 weeks of gestation were included in the analysis. The incidence of all pregnancy-related hypertensive conditions, diagnosis of severe hypertensive conditions (hemolysis, elevated liver enzymes and low platelets syndrome; disseminated intravascular coagulation; eclampsia; low platelets; renal failure; and abruption), and interventional delivery related to hypertension were estimated, and compared according to fetal number. RESULTS Data were analyzed for 34,374 singleton, twin, triplet, and quadruplet gestations. The incidence of pregnancy-related hypertensive conditions increased with multifetal gestations as compared with singletons (12.7-19.6% for multifetal gestations compared with 6.5% for singletons, P < .001). The incidence of severe pregnancy-related hypertensive conditions was significantly increased in twin (1.6%) and triplet (3.1%) gestations as compared with singletons (0.5%, P < .001). Quadruplet pregnancies were not significantly higher than triplet gestations for these complications. The need for early delivery related to hypertension was greater with increasing fetal number through triplet gestations. By logistic regression, higher fetal number, nulliparity, and advanced maternal age were each independently associated with the development of pregnancy-related hypertensive conditions. CONCLUSION Mild and severe pregnancy-related hypertensive disease increases progressively with advancing fetal number from singleton to triplets but is not further increased in quadruplet pregnancies. Multifetal pregnancies should be observed closely for onset of gestational hypertensive disease. LEVEL OF EVIDENCE II-2.

IntroductionThe spectrum of disease resulting from the pathophysiology of preeclampsia continues to challenge the diagnostic acumen of clinicians. One of preeclampsia's various manifestations includes the specific entity of HELLP syndrome. Recently, investigators have provided evidence some case

Objective Inadequate data describe pancreatitis as a complication in women with acute fatty liver of pregnancy. Our purpose was to report our experience with this complication, which included maternal and perinatal outcomes. Study design Medical records of patients with acute fatty liver of pregnancy and/or pancreatitis were reviewed over a 15-year period. Records were reviewed for symptoms, laboratory findings, clinical course, and maternal and perinatal outcomes. Results Persistent nausea and vomiting were the symptoms in 10 of 12 patients (83%). The average maternal age was 26.3 years (range, 21-37 years). There were two maternal deaths (17%); one death occurred despite liver transplantation. Maternal morbidity included encephalopathy (50%), acute respiratory distress syndrome (17%), and renal failure (33%) that resulted from acute tubular necrosis (3 cases) and acute cortical necrosis (1 case) that required renal transplantation. Of the 12 patients, 11 patients (91%) had an elevated serum lipase level, and another patient had an elevated serum amylase level (9%). Eight of 12 patients (67%) underwent radiologic studies, of which 7 patients (88%) were diagnostic for pancreatitis. Radiographic and autopsy findings noted pancreatic inflammation (3 cases), pseudocyst formation (3 cases), and hemorrhagic pancreatitis (1 case). The radiographic and serum laboratory abnormalities occurred after the onset of hepatic and renal abnormalities in all cases. Conclusion Pancreatitis is a potentially lethal complication of acute fatty liver of pregnancy, and all patients with this diagnosis should undergo screening for the abnormality. Pancreatic abnormalities typically appear after hepatic and renal dysfunction.

Objective: This study was performed to evaluate a protocol for treatment of previable premature rupture of membranes (PROM) that includes the administration of gelatin sponge to retard the loss of fluid from the amniotic cavity. Study Design: Women with PROM at ≤21 weeks' gestation with a structurally normal singleton; having no evidence of infection, active bleeding, or labor; and a maximum vertical fluid pocket of less than 1.5 cm were candidates. Interventions included hospital admission, amnioinfusion, cervical cerclage, administration of gelatin sponge (Gelfoam) into the amniotic cavity, antibiotic administration, and perioperative tocolysis. Weekly assessment of fluid status was performed and if oligohydramnios returned, patients were offered repeat amnioinfusion. Results: Fifteen women with PROM at 17.9 ± 2.2 weeks' gestation (range 13-21 weeks) underwent this protocol. Spontaneous PROM was diagnosed in 14 patients and one had iatrogenic PROM after fetoscopy. Eight fetuses reached a viable gestational age (≥24 weeks, 53%), with six of these newborn infants surviving to hospital discharge (30%) and two suffering intrauterine death. The average gestational age of delivery for survivors was 31.8 ± 4.3 weeks, range 25 to 36 weeks. Talipes equivarus was observed in three survivors (50%). Bilateral hip dysplasia and torticollis were also diagnosed in two infants. Respiratory distress syndrome was diagnosed in all cases delivered at less than 32 weeks but was not observed thereafter. No adverse sequelae have been attributed to gelatin sponge exposure. Conclusion: The observed survival rate with this interventional approach in a population at highest risk for pregnancy loss justifies further study of this treatment strategy. This protocol may not reduce the rate of musculoskeletal abnormalities. (Am J Obstet Gynecol 2002;187:1143-6.)

Objective The purpose of this study was to evaluate the utility of ultrasound surveillance after cerclage placement and to propose a rationale for cervical sonography in this setting. Subjects and methods This was a retrospective analysis of 53 women undergoing cervical cerclage by a maternal-fetal medicine specialist, regardless of indication, and delivering between January 1999 and April 2001. Transvaginal ultrasonographic assessment of cervical length and the degree of cervical funneling after cerclage were compared to preoperative values and to outcomes including gestational age at delivery. Funneling to the cerclage was defined as membranes prolapsing down the endocervical canal until they reached the plane of the cerclage. Results Cervical cerclage resulted in a significant increase in cervical length from 2.1 ± 1.2 cm to 2.9 ± 0.8 cm after the procedure, P < 0.001; however, this measure was not correlated with gestational age at delivery. Funneling to the level of the cerclage was associated with an earlier gestational age at delivery 31.3 ± 5.6 weeks vs. 36.8 ± 2.8 weeks for those cases without this finding, P < 0.001. A statistically significant association between funneling to the cerclage and preterm delivery was identified irrespective of the indication (prophylactic or emergency) for the procedure. When descent of the membranes to the level of the cerclage was noted, it occurred by 28 weeks' gestation in all patients studied. The incidence of premature rupture of the membranes was also significantly greater postcerclage in women with descent of the membranes to the cerclage (52%) compared to those without this finding (9%) P = 0.002. Conclusions Funneling to the cerclage is significantly associated with earlier preterm delivery in patients who have undergone cervical cerclage. Serial sonography up to 28 weeks' gestation is useful in identifying patients at higher risk for premature rupture of the membranes and preterm delivery. Copyright © 2002 International Society of Ultrasound in Obstetrics and Gynecology