Antenatal depressive symptoms are strongly predicted by the severity of pre-menstrual syndrome: results of partial least squares analysis

Background/Objective: Antenatal depression (AD) is the commonest morbidity during pregnancy. There is evidence that premenstrual syndrome (PMS) and AD share common immune-inflammatory and sex hormonal pathways. This study aims to evaluate the association between the severity of depressive PMS and AD in early and late pregnancy. Method: Participants were followed from early (<=16 weeks) to late pregnancy (>=20 weeks). The Premenstrual Symptoms Screening Tool (PSST) was used to assess PMS and AD symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS). Results: Up to 57.6% of the variance in the early EPDS score was explained by the regression on the first factor extracted from 10 depression and anxiety PSST items (dubbed the DepAnx PSST), insomnia PSST, relation dissatisfaction, and partner abuse. There were specific indirect effects of DepAnx PSST (p < 0.001), insomnia PSST (p = 0.041), relation dissatisfaction (p = 0.023) and partner abuse (p = 0.007) on the late EPDS which were mediated by the early EPDS score. Conclusion: The affective, but not psychosomatic, symptoms of PMS strongly predict AD symptoms suggesting that the pathophysiology of affective PMS symptoms overlap with those of AD. (AU)

Antenatal depressive symptoms are strongly predicted by the severity of pre-menstrual syndrome: results of partial least squares analysis.

BACKGROUND/OBJECTIVE: Antenatal depression (AD) is the commonest morbidity during pregnancy. There is evidence that premenstrual syndrome (PMS) and AD share common immune-inflammatory and sex hormonal pathways. This study aims to evaluate the association between the severity of depressive PMS and AD in early and late pregnancy. METHOD: Participants were followed from early (<=16 weeks) to late pregnancy (>=20 weeks). The Premenstrual Symptoms Screening Tool (PSST) was used to assess PMS and AD symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS). RESULTS: Up to 57.6% of the variance in the early EPDS score was explained by the regression on the first factor extracted from 10 depression and anxiety PSST items (dubbed the DepAnx PSST), insomnia PSST, relation dissatisfaction, and partner abuse. There were specific indirect effects of DepAnx PSST (p < 0.001), insomnia PSST (p = 0.041), relation dissatisfaction (p = 0.023) and partner abuse (p = 0.007) on the late EPDS which were mediated by the early EPDS score. CONCLUSION: The affective, but not psychosomatic, symptoms of PMS strongly predict AD symptoms suggesting that the pathophysiology of affective PMS symptoms overlap with those of AD.

Barriers and Facilitators to Implementing Immediate Postpartum Contraceptive Implant Programs: A Formative Implementation Research.

Objective: This study sought to identify the factors that act as barriers and facilitators to developing and implementing Immediate postpartum (IPP) insertion of contraceptive implants service according to the Consolidated Framework for Implementation Research (CFIR). Methods: We conducted in-depth interviews and focus group discussions to explore IPP contraceptive implantation programs implemented in community, regional, and university hospitals in Thailand. The CFIR was used to guide the data collection and analyses. Results: All CFIR domains were found to have an impact on planning and implementation. Out of 38 constructs, nine were identified as either barriers or facilitators, and four were determined to be both. Barriers included an insufficient training budget, lack of policy to support non-teenagers, disconnect among organizations, and lack of knowledge on the part of the clients. Facilitators included the relative advantage of implants over other contraceptive methods, reimbursement policy, laws that promote teenage autonomy, setting IPP implants as a key performance indicator (KPI), identifying project champions, and educating clients through antenatal counseling or multimedia intervention. Conclusion: Barriers and facilitators to the successful implementation of an IPP contraceptive implant program were identified. In order to successfully implement this service, modifiable barriers should be overcome and facilitators should be strengthened. Strategies tailored to the local context should be developed to ensure the sustainability of the program. Educating clients is crucial and need both hospital- and community interventions.

Adverse childhood experiences combined with emotional and physical abuse by the partner predict antenatal depression.

BACKGROUND: Few studies examined the contributions of childhood adversities, intimate partner violence and social support to antenatal depression (AD). This study aims to 1) evaluate association of these psychosocial factors with AD symptoms in pregnancy; and 2) examine the mediating effect of social support on the relationship between psychosocial stressors and AD symptoms. METHODS: Participants were 120 pregnant women aged from 18 to 49 in less than 16 gestational weeks and attending at Antenatal Care Center at Khon Kaen hospital, Thailand. AD symptoms were assessed by the Edinburgh Postnatal Depression Scale (EPDS). Childhood adversities, intimate partner violence and social support were measured using the Adverse Childhood Experiences Questionnaire (ACE questionnaire), Abuse Assessment Screen (AAS), and Multidimensional Scale of Perceived Social Support (MSPSS). RESULTS: We found that the EPDS score was significantly and positively associated with adverse childhood experiences (ACEs) and negatively with social support. Partial Least Square analysis showed that 49.1% of the variance in the depressive subdomain of the EPDS score was predicted by ACEs, namely psychological and physical abuse and neglect, emotional or physical abuse by the partner, unplanned pregnancy, and no satisfaction with their relationship. The effects of adverse childhood experience due to neglect on the EDPS score was mediated by social support by friends. LIMITATIONS: ACEs were assessed retrospectively and, therefore, may be susceptible to recall bias. CONCLUSION: Prenatal depression scores are to a large extent predicted by psychological distress as indicated by early lifetime trauma, abuse by partner, relation satisfaction, and implications of unintended pregnancy.

Progestogens or progestogen-releasing intrauterine systems for uterine fibroids (other than preoperative medical therapy).

BACKGROUND: Uterine fibroids can cause heavy menstrual bleeding. Medical treatments are considered to preserve fertility. It is unclear whether progestogens or progestogen-releasing intrauterine systems can reduce fibroid-related symptoms. This is the first update of a Cochrane Review published in 2013. OBJECTIVES: To determine the effectiveness of progestogens or progestogen-releasing intrauterine systems in treating premenopausal women with uterine fibroids. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, and PsycINFO databases to July 2020. We also searched trials registers for ongoing and registered trials, and checked references of relevant trials. SELECTION CRITERIA: All identified published or unpublished randomised controlled trials (RCTs) assessing the effect of progestogens or progestogen-releasing intrauterine systems in treating premenopausal women with uterine fibroids. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data, assessed risk of bias, and assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: This updated review included four studies with 221 women with uterine fibroids. The evidence was very low quality, downgraded for serious risk of bias, due to poor reporting of study methods, and serious imprecision. Levonorgestrel-releasing intrauterine device (LNG-IUS) versus hysterectomy There was no information on the outcomes of interest, including adverse events. LNG-IUS versus low dose combined oral contraceptive (COC) At 12 months, we are uncertain whether LNG-IUS reduced the percentage of abnormal uterine bleeding, measured with the alkaline hematin test (mean difference (MD) 77.50%, 95% confidence interval (CI) 70.44 to 84.56; 1 RCT, 44 women; very low-quality evidence), or the pictorial blood assessment chart (PBAC; MD 34.50%, 95% CI 11.59 to 57.41; 1 RCT, 44 women; very low-quality evidence); increased haemoglobin levels (MD 1.50 g/dL, 95% CI 0.85 to 2.15; 1 RCT, 44 women; very low-quality evidence), or reduced fibroid size more than COC (MD 1.90%, 95% CI -12.24 to 16.04; 1 RCT, 44 women; very low-quality evidence). The study did not measure adverse events. LNG-IUS versus oral progestogen (norethisterone acetate (NETA)) Compared to NETA, we are uncertain whether LNG-IUS reduced abnormal uterine bleeding more from baseline to six months (visual bleeding score; MD 23.75 points, 95% CI 1.26 to 46.24; 1 RCT, 45 women; very low-quality evidence); increased the percentage of change in haemoglobin from baseline to three months (MD 4.53%, 95% CI 1.46 to 7.60; 1 RCT, 48 women; very low-quality evidence), or from baseline to six months (MD 10.14%, 95% CI 5.57 to 14.71; 1 RCT, 45 women; very low-quality evidence). The study did not measure fibroid size. Spotting (adverse event) was more likely to be reported by women with the LNG-IUS (64.3%) than by those taking NETA (30%; 1 RCT, 45 women; very low-quality evidence). Oral progestogen (dienogest, desogestrel) versus goserelin acetate Compared to goserelin acetate, we are uncertain whether abnormal uterine bleeding was reduced at 12 weeks with dienogest (PBAC; MD 216.00 points, 95% CI 149.35 to 282.65; 1 RCT, 14 women; very low-quality evidence) or desogestrel (PBAC; MD 78.00 points, 95% CI 28.94 to 127.06; 1 RCT, 16 women; very low-quality evidence). Vasomotor symptoms (adverse events, e.g. hot flashes) are only associated with goserelin acetate (55%), not with dienogest (1 RCT, 14 women; very low-quality evidence) or with desogestrel (1 RCT, 16 women; very low-quality evidence). The study did not report fibroid size. AUTHORS' CONCLUSIONS: Because of very low-quality evidence, we are uncertain whether the LNG-IUS reduces abnormal uterine bleeding or increases haemoglobin levels in premenopausal women with uterine fibroids, compared to COC or norethisterone acetate. There was insufficient evidence to determine whether the LNG-IUS reduces the size of uterine fibroids compared to COC. We are uncertain whether oral progestogens reduce abnormal uterine bleeding as effectively as goserelin acetate, but women reported fewer adverse events, such as hot flashes.

Alternative Magnesium Sulfate Dosing Regimens for Women With Preeclampsia: A Population Pharmacokinetic Exposure-Response Modeling and Simulation Study.

Magnesium sulfate is the anticonvulsant of choice for eclampsia prophylaxis and treatment; however, the recommended dosing regimens are costly and cumbersome and can be administered only by skilled health professionals. The objectives of this study were to develop a robust exposure-response model for the relationship between serum magnesium exposure and eclampsia using data from large studies of women with preeclampsia who received magnesium sulfate, and to predict eclampsia probabilities for standard and alternative (shorter treatment duration and/or fewer intramuscular injections) regimens. Exposure-response modeling and simulation were applied to existing data. A total of 10 280 women with preeclampsia who received magnesium sulfate or placebo were evaluated. An existing population pharmacokinetic model was used to estimate individual serum magnesium exposure. Logistic regression was applied to quantify the serum magnesium area under the curve-eclampsia rate relationship. Our exposure-response model-estimated eclampsia rates were comparable to observed rates. Several alternative regimens predicted magnesium peak concentration < 3.5 mmol/L (empiric safety threshold) and eclampsia rate ≤ 0.7% (observed response threshold), including 4 g intravenously plus 10 g intramuscularly followed by either 8 g intramuscularly every 6 hours × 3 doses or 10 g intramuscularly every 8 hours × 2 doses and 10 g intramuscularly every 8 hours × 3 doses. Several alternative magnesium sulfate regimens with comparable model-predicted efficacy and safety were identified that merit evaluation in confirmatory clinical trials.

Population Pharmacokinetic Modeling to Evaluate Standard Magnesium Sulfate Treatments and Alternative Dosing Regimens for Women With Preeclampsia.

Magnesium sulfate is the standard therapy for prevention and treatment of eclampsia. Two standard dosing regimens require either continuous intravenous infusion or frequent, large-volume intramuscular injections, which may preclude patients from receiving optimal care. This project sought to identify alternative, potentially more convenient, but similarly effective dosing regimens that could be used in restrictive clinical settings. A 2-compartment population pharmacokinetic (PK) model was developed to characterize serial PK data from 92 pregnant women with preeclampsia who received magnesium sulfate. Body weight and serum creatinine concentration had a significant impact on magnesium PK. The final PK model was used to simulate magnesium concentration profiles for the 2 standard regimens and several simplified alternative dosing regimens. The simulations suggest that intravenous regimens with loading doses of 8 g over 60 minutes followed by 2 g/h for 10 hours and 12 g over 120 minutes followed by 2 g/h for 8 hours (same total dose as the standard intravenous regimen but shorter treatment duration) would result in magnesium concentrations below the toxic range. For the intramuscular regimens, higher maintenance doses given less frequently (4 g intravenously + 10-g intramuscular loading doses with maintenance doses of 8 g every 6 hours or 10 g every 8 hours for 24 hours) or removal of the intravenous loading dose (eg, 10 g intramusculary every 8 hours for 24 hours) may be reasonable alternatives. In addition, individualized dose adjustments based on body weight and serum creatinine were proposed for the standard regimens.

Association of antibody to E2 protein of human papillomavirus and p16INK4A with progression of HPV-infected cervical lesions.

Human papillomavirus (HPV) E2 and L1 proteins are expressed in cervical cells during the lytic stage of infection. Overexpression of p16INK4A is a biomarker of HPV-associated cervical neoplasia. This study investigated antibodies to HPV16 E2, HPV16 L1, and p16INK4A in sera from women with no squamous intraepithelial lesion (No-SIL) of the cervix, low-grade SIL, high-grade SIL, and cervical squamous cell carcinoma (SCC). HPV DNA was detected by polymerase chain reaction. Anti-E2, -L1, and -p16INK4A antibodies in sera were determined by western blot. Among 116 samples, 69 (60%) were HPV DNA-positive. Percentages seropositive for anti-E2, -L1, and -p16INK4A antibodies were 39.6, 22.4, and 23.3%, respectively. Anti-E2 antibody was significantly correlated with HPV DNA-positive cases. Eighty-seven women (75%) were regarded as infected with HPV, having at least one positive result from HPV DNA, L1, or E2 antibody. Antibody to p16INK4A was associated with HPV infection (odds = 5.444, 95% CI 1.203-24.629, P = 0.028) and precancerous cervical lesions (odds = 5.132, 95% CI 1.604-16.415, P = 0.006). Interestingly, the concurrent detection of anti-E2 and -p16INK4A antibodies was significantly associated with HPV infection (odds = 1.382, 95% CI 1.228-1.555, P = 0.044). These antibodies might be good candidate biomarkers for monitoring HPV-associated cervical lesion development to cancer.

Cesarean rates and severe maternal and neonatal outcomes according to the Robson 10-Group Classification System in Khon Kaen Province, Thailand.

OBJECTIVE: To assess cesarean rates and maternal and neonatal outcomes in each group in the Robson 10-Group Classification System (TGCS). METHODS: In a cross-sectional study, data were reviewed from all pregnant women who delivered at 24 government hospitals in Khon Kaen Province, Thailand, in 2014. Delivery and perinatal outcomes were recorded. RESULTS: Of 18 043 deliveries, 5666 (31.4%) were by cesarean. Women in group 5 (previous cesarean) accounted for the most cesareans (1472, 26.0%). Groups 1 and 2 (nulliparous women) accounted for 2355 (41.6%) of procedures; the rate of cesarean within these two groups was 19.4% (1162/5981) and 71.2% (1193/1675), respectively. As compared with group 1, women in groups 2, 4, 6, 7, and 10 had significantly increased risk of severe maternal outcomes, and those in groups 6, 7, 8, 9, and 10 had an increased risk of severe neonatal outcomes. CONCLUSION: The rate of cesarean in the study setting was high, and three out of four procedures were performed for women in groups 5, 1, and 2. Interventions should be focused on these groups to reduce the overall cesarean rates.

Correlation of Circulating CD64+/CD163+ Monocyte Ratio and stroma/peri-tumoral CD163+ Monocyte Density with Human Papillomavirus Infected Cervical Lesion Severity.

HPV infected cervical cells secrete mediators that are gradually changed and have influence on infiltrating M2 phenotypic monocytes in cervical lesions. However, profiles of circulating immune cells in women with cervical lesions and M2 phenotypic monocyte activity in HPV infected cervical lesions are limited. This study aimed to investigate circulating monocyte populations correlated with M2 phenotype density and its activity in HPV infected cervical lesions. HPV DNA was investigated in cervical tissues using PCR. High risk HPV E6/E7 mRNA was detected using in situ hybridization. CD163 immunohistochemical staining was performed for M2 macrophage. CD163 and Arg1 mRNA expression were detected using real-time PCR. Circulating monocyte subpopulations were analyzed using flow cytometry. CD163 and Arg1 mRNA expression were increased according to cervical lesion severity and corresponding with density of M2 macrophage in HSIL and SCC in stroma and peri-tumoral areas. Additionally, the relationship between M2 macrophage infiltration and high risk HPV E6/E7 mRNA expression was found and corresponded with cervical lesion severity. Circulating CD14+CD16+ and CD14+CD163+ monocytes were elevated in No-SIL and cervical lesions. Interestingly, CD14+CD64+ monocyte was greatly elevated in HSIL and SCC, whereas intracellular IL-10+ monocytes were not significantly different between cervical lesions. The correlation between increasing ratio of circulating CD64+/CD163+ monocyte and density of infiltrating CD163+ monocytes was associated with severity of HPV infected cervical lesions. The elevated circulating CD64+/CD163+ monocyte ratio correlates to severity of HPV infected cervical lesions and might be a prognostic marker in cervical cancer progression.

Dietary supplements for dysmenorrhoea.

BACKGROUND: Dysmenorrhoea refers to painful menstrual cramps and is a common gynaecological complaint. Conventional treatments include non-steroidal anti-inflammatory drugs (NSAIDs) and oral contraceptive pills (OCPs), which both reduce myometrial activity (contractions of the uterus). A suggested alternative approach is dietary supplements. We used the term 'dietary supplement' to include herbs or other botanical, vitamins, minerals, enzymes, and amino acids. We excluded traditional Chinese medicines. OBJECTIVES: To determine the efficacy and safety of dietary supplements for treating dysmenorrhoea. SEARCH METHODS: We searched sources including the Cochrane Gynaecology and Fertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, AMED, PsycINFO (all from inception to 23 March 2015), trial registries, and the reference lists of relevant articles. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of dietary supplements for moderate or severe primary or secondary dysmenorrhoea. We excluded studies of women with an intrauterine device. Eligible comparators were other dietary supplements, placebo, no treatment, or conventional analgesia. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, performed data extraction and assessed the risk of bias in the included trials. The primary outcomes were pain intensity and adverse effects. We used a fixed-effect model to calculate odds ratios (ORs) for dichotomous data, and mean differences (MDs) or standardised mean differences (SMDs) for continuous data, with 95% confidence intervals (CIs). We presented data that were unsuitable for analysis either descriptively or in additional tables. We assessed the quality of the evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods. MAIN RESULTS: We included 27 RCTs (3101 women). Most included studies were conducted amongst cohorts of students with primary dysmenorrhoea in their late teens or early twenties. Twenty-two studies were conducted in Iran and the rest were performed in other middle-income countries. Only one study addressed secondary dysmenorrhoea. Interventions included 12 different herbal medicines (German chamomile (Matricaria chamomilla, M recutita, Chamomilla recutita), cinnamon (Cinnamomum zeylanicum, C. verum), Damask rose (Rosa damascena), dill (Anethum graveolens), fennel (Foeniculum vulgare), fenugreek (Trigonella foenum-graecum), ginger (Zingiber officinale), guava (Psidium guajava), rhubarb (Rheum emodi), uzara (Xysmalobium undulatum), valerian (Valeriana officinalis), and zataria (Zataria multiflora)) and five non-herbal supplements (fish oil, melatonin, vitamins B1 and E, and zinc sulphate) in a variety of formulations and doses. Comparators included other supplements, placebo, no treatment, and NSAIDs.We judged all the evidence to be of low or very low quality. The main limitations were imprecision due to very small sample sizes, failure to report study methods, and inconsistency. For most comparisons there was only one included study, and very few studies reported adverse effects. Effectiveness of supplements for primary dysmenorrhoea We have presented pain scores (all on a visual analogue scale (VAS) 0 to 10 point scale) or rates of pain relief, or both, at the first post-treatment follow-up. Supplements versus placebo or no treatmentThere was no evidence of effectiveness for vitamin E (MD 0.00 points, 95% CI -0.34 to 0.34; two RCTs, 135 women).There was no consistent evidence of effectiveness for dill (MD -1.15 points, 95% CI -2.22 to -0.08, one RCT, 46 women), guava (MD 0.59, 95% CI -0.13 to 1.31; one RCT, 151 women); one RCT, 73 women), or fennel (MD -0.34 points, 95% CI -0.74 to 0.06; one RCT, 43 women).There was very limited evidence of effectiveness for fenugreek (MD -1.71 points, 95% CI -2.35 to -1.07; one RCT, 101 women), fish oil (MD 1.11 points, 95% CI 0.45 to 1.77; one RCT, 120 women), fish oil plus vitamin B1 (MD -1.21 points, 95% CI -1.79 to -0.63; one RCT, 120 women), ginger (MD -1.55 points, 95% CI -2.43 to -0.68; three RCTs, 266 women; OR 5.44, 95% CI 1.80 to 16.46; one RCT, 69 women), valerian (MD -0.76 points, 95% CI -1.44 to -0.08; one RCT, 100 women), vitamin B1 alone (MD -2.70 points, 95% CI -3.32 to -2.08; one RCT, 120 women), zataria (OR 6.66, 95% CI 2.66 to 16.72; one RCT, 99 women), and zinc sulphate (MD -0.95 points, 95% CI -1.54 to -0.36; one RCT, 99 women).Data on chamomile and cinnamon versus placebo were unsuitable for analysis. Supplements versus NSAIDSThere was no evidence of any difference between NSAIDs and dill (MD 0.13 points, 95% CI -1.01 to 1.27; one RCT, 47 women), fennel (MD -0.70 points, 95% CI -1.81 to 0.41; one RCT, 59 women), guava (MD 1.19, 95% CI 0.42 to 1.96; one RCT, 155 women), rhubarb (MD -0.20 points, 95% CI -0.44 to 0.04; one RCT, 45 women), or valerian (MD points 0.62 , 95% CI 0.03 to 1.21; one RCT, 99 women),There was no consistent evidence of a difference between Damask rose and NSAIDs (MD -0.15 points, 95% CI -0.55 to 0.25; one RCT, 92 women).There was very limited evidence that chamomile was more effective than NSAIDs (MD -1.42 points, 95% CI -1.69 to -1.15; one RCT, 160 women). Supplements versus other supplementsThere was no evidence of a difference in effectiveness between ginger and zinc sulphate (MD 0.02 points, 95% CI -0.58 to 0.62; one RCT, 101 women). Vitamin B1 may be more effective than fish oil (MD -1.59 points, 95% CI -2.25 to -0.93; one RCT, 120 women). Effectiveness of supplements for secondary dysmenorrhoea There was no strong evidence of benefit for melatonin compared to placebo for dysmenorrhoea secondary to endometriosis (data were unsuitable for analysis). Safety of supplements Only four of the 27 included studies reported adverse effects in both treatment groups. There was no evidence of a difference between the groups but data were too scanty to reach any conclusions about safety. AUTHORS' CONCLUSIONS: There is no high quality evidence to support the effectiveness of any dietary supplement for dysmenorrhoea, and evidence of safety is lacking. However for several supplements there was some low quality evidence of effectiveness and more research is justified.

Pharmacological interventions for generalised itching (not caused by systemic disease or skin lesions) in pregnancy.

BACKGROUND: Generalised itching is one of the most common dermatological symptoms in pregnant women. Having itchy skin during pregnancy may be very frustrating and can lead to poor sleep, exhaustion and impaired quality of life. There is a need for a systematic review to evaluate the effectiveness and safety of pharmacological interventions for treating itching in pregnancy. OBJECTIVES: To assess the effectiveness and safety of pharmacological interventions for treating generalised itching (not caused by systemic diseases or skin lesions) in pregnancy. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 January 2016) and the reference list of the one identified study. SELECTION CRITERIA: All published, unpublished and ongoing randomised controlled trials (RCTs) evaluating interventions for itching in pregnancy.Quasi-RCTs, cluster-RCTs, RCTs using a cross-over design, and studies reported in abstract form (without full text) were not eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the one trial report that was identified from the search strategy and this was subsequently excluded. MAIN RESULTS: There are no included studies as we did not identify any relevant trials. AUTHORS' CONCLUSIONS: Generalised itching (not caused by systemic disease or skin lesions) is quite a common symptom in pregnancy. However, there is no evidence from randomised controlled trials to guide practice in terms of the effectiveness and safety of pharmacological interventions for treating this condition.Well-designed randomised controlled trials are needed in order to evaluate the effectiveness of topical and systemic pharmacological interventions as well as any adverse effects of the interventions. Such studies should consider important outcomes such as relief of itching, women's satisfaction, sleep disturbance, and adverse effects.

Interventions for treating constipation in pregnancy.

BACKGROUND: Constipation is a common symptom experienced during pregnancy. It has a range of consequences from reduced quality of life and perception of physical health to haemorrhoids. An understanding of the effectiveness and safety of treatments for constipation in pregnancy is important for the clinician managing pregnant women. OBJECTIVES: To assess the effectiveness and safety of interventions (pharmacological and non-pharmacological) for treating constipation in pregnancy. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2015), ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (30 April 2015) and reference lists of retrieved studies. SELECTION CRITERIA: We considered all published, unpublished and ongoing randomised controlled trials (RCTs), cluster-RCTs and quasi-RCTs, evaluating interventions (pharmacological and non-pharmacological) for constipation in pregnancy. Cross-over studies were not eligible for inclusion in this review. Trials published in abstract form only (without full text publication) were not eligible for inclusion.We compared one intervention (pharmacological or non-pharmacological) against another intervention, placebo or no treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: Four studies were included, but only two studies with a total of 180 women contributed data to this review. It was not clear whether they were RCTs or quasi-RCTs because the sequence generation was unclear. We classified the overall risk of bias of three studies as moderate and one study as high risk of bias. No meta-analyses were carried out due to insufficient data.There were no cluster-RCTs identified for inclusion. Comparisons were available for stimulant laxatives versus bulk-forming laxatives, and fibre supplementation versus no intervention. There were no data available for any other comparisons.During the review process we found that studies reported changes in symptoms in different ways. To capture all data available, we added a new primary outcome (improvement in constipation) - this new outcome was not prespecified in our published protocol. Stimulant laxatives versus bulk-forming laxativesNo data were identified for any of this review's prespecified primary outcomes: pain on defecation, frequency of stools and consistency of stools.Compared to bulk-forming laxatives, pregnant women who received stimulant laxatives had significantly more improvement in constipation (risk ratio (RR) 1.59, 95% confidence interval (CI) 1.21 to 2.09; 140 women, one study, moderate quality of evidence), but also significantly more abdominal discomfort (RR 2.33, 95% CI 1.15 to 4.73; 140 women, one study, low quality of evidence), and borderline difference in diarrhoea (RR 4.50, 95% CI 1.01 to 20.09; 140 women, one study, moderate quality of evidence). In addition, there was no significant difference in women's satisfaction (RR 1.06, 95% CI 0.77 to 1.46; 140 women, one study, moderate quality of evidence).No usable data were identified for any of this review's secondary outcomes: quality of life; dehydration; electrolyte imbalance; acute allergic reaction; or asthma. Fibre supplementation versus no interventionPregnant women who received fibre supplementation had significantly higher frequency of stools compared to no intervention (mean difference (MD) 2.24 times per week, 95% CI 0.96 to 3.52; 40 women, one study, moderate quality of evidence). Fibre supplementation was associated with improved stool consistency as defined by trialists (hard stool decreased by 11% to 14%, normal stool increased by 5% to 10%, and loose stool increased by 0% to 6%).No usable data were reported for either the primary outcomes of pain on defecation and improvement in constipation or any of this review's secondary outcomes as listed above. Quality Five outcomes were assessed with the GRADE software: improvement in constipation, frequency of stools, abdominal discomfort, diarrhoea and women's satisfaction. These were assessed to be of moderate quality except for abdominal discomfort which was assessed to be of low quality. The results should therefore be interpreted with caution. There were no data available for evaluation of pain on defecation or consistency of stools. AUTHORS' CONCLUSIONS: There is insufficient evidence to comprehensively assess the effectiveness and safety of interventions (pharmacological and non-pharmacological) for treating constipation in pregnancy, due to limited data (few studies with small sample size and no meta-analyses). Compared with bulk-forming laxatives, stimulant laxatives appear to be more effective in improvement of constipation (moderate quality evidence), but are accompanied by an increase in diarrhoea (moderate quality evidence) and abdominal discomfort (low quality evidence) and no difference in women's satisfaction (moderate quality evidence). Additionally, fibre supplementation may increase frequency of stools compared with no intervention (moderate quality evidence), although these results were of moderate risk of bias.There were no data for a comparison of other types of interventions, such as osmotic laxatives, stool softeners, lubricant laxatives and enemas and suppositories.More RCTs evaluating interventions for treating constipation in pregnancy are needed. These should cover different settings and evaluate the effectiveness of various interventions (including fibre, osmotic, and stimulant laxatives) on improvement in constipation, pain on defecation, frequency of stools and consistency of stools.

Antenatal lower genital tract infection screening and treatment programs for preventing preterm delivery.

BACKGROUND: Genital tract infection is associated with preterm birth (before 37 weeks' gestation). Screening for infections during pregnancy may therefore reduce the numbers of babies being born prematurely. However, screening for infections may have some adverse effects, such as increased antibiotic drug resistance and increased cost of treatment. OBJECTIVES: To assess the effectiveness of antenatal lower genital tract infection screening and treatment programs for reducing preterm birth and subsequent morbidity. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 November 2014), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2014, Issue 7) and reference lists of retrieved reports. SELECTION CRITERIA: We included all published and unpublished randomised controlled trials in any language that evaluated any described methods of antenatal lower genital tract infection screening compared with no screening. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked for accuracy. MAIN RESULTS: One study (4155 women at less than 20 weeks' gestation) met the inclusion criteria. The intervention group (2058 women) received infection screening and treatment for bacterial vaginosis, trichomonas vaginalis and candidiasis; the control group (2097 women) also received screening, but the results of the screening program were not revealed and women received routine antenatal care. The rate of preterm birth before 37 weeks' gestation was significantly lower in the intervention group (3% versus 5% in the control group) with a risk ratio (RR) of 0.55 (95% confidence interval (CI) 0.41 to 0.75; the evidence for this outcome was graded as of moderate quality). The incidence of preterm birth for infants with a weight equal to or below 2500 g (low birthweight) and infants with a weight equal to or below 1500 g (very low birthweight) were significantly lower in the intervention group than in the control group (RR 0.48, 95% CI 0.34 to 0.66 and RR 0.34; 95% CI 0.15 to 0.75, respectively; both graded as moderate quality evidence). Based on a subset of costs for preterm births of < 1900 g, the authors reported that for each of those preterm births averted, EUR 60,262 would be saved. AUTHORS' CONCLUSIONS: There is evidence from one trial that infection screening and treatment programs for pregnant women before 20 weeks' gestation reduce preterm birth and preterm low birthweight. Infection screening and treatment programs are associated with cost savings when used for the prevention of preterm birth. Future trials should evaluate the effects of different types of infection screening programs.

Hepatitis B vaccination during pregnancy for preventing infant infection.

BACKGROUND: Infant hepatitis B infection increases the risk of chronic infection, cirrhosis or liver cancer (hepatocellular carcinoma) in the adult. Perinatal transmission is a common route of infection. OBJECTIVES: To assess the effectiveness and adverse effects of hepatitis B vaccine administered to pregnant women for preventing hepatitis B virus infection in infants. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2014). SELECTION CRITERIA: Randomized controlled trials (RCTs) assessing hepatitis B vaccination compared with placebo or no treatment during pregnancy for preventing infant infection. Quasi-RCTs and cross-over studies were not eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion. If any studies had been included, we planned to assess the risk of bias, extract data and check the data for accuracy of all included studies. MAIN RESULTS: We did not identify any studies for inclusion. AUTHORS' CONCLUSIONS: We found no RCTs that assessed the effects of hepatitis B vaccine during pregnancy for preventing infant infection. Consequently, this review cannot provide guidance for clinical practice in this area. However, it does identify the need for well-designed randomized clinical trials to assess the effect of hepatitis B vaccine during pregnancy on the incidence of infant infection and to determine any adverse effects.

Antibiotics for meconium-stained amniotic fluid in labour for preventing maternal and neonatal infections.

BACKGROUND: Chorioamnionitis is more likely to occur when meconium-stained amniotic fluid (MSAF) is present. Meconium may enhance the growth of bacteria in amniotic fluid by serving as a growth factor, inhibiting bacteriostatic properties of amniotic fluid. Many adverse neonatal outcomes related to MSAF result from meconium aspiration syndrome (MAS). MSAF is associated with both maternal and newborn infections. Antibiotics may be an effective option to reduce such morbidity. OBJECTIVES: The objective of this review is to assess the efficacy and side effects of prophylactic antibiotics for MSAF during labour in preventing maternal and neonatal infections. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2014).  SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing prophylactic antibiotics with placebo or no treatment during labour for women with MSAF. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: We included two studies with 362 pregnant women. Both studies compared ampicillin-sulbactam (N = 183) versus normal saline (N = 179) in pregnant women with MSAF. Prophylactic antibiotics appeared to have no statistically significant reduction in the incidence of neonatal sepsis (risk ratio (RR) 1.00, 95% CI 0.21 to 4.76), neonatal intensive care unit (NICU) admission (RR 0.83, 95% CI 0.39 to 1.78) and postpartum endometritis (RR 0.50, 95% CI 0.18 to 1.38). However, there was a significant decrease in the risk of chorioamnionitis (RR 0.36, 95% CI 0.21 to 0.62). No serious adverse effects were reported. Drug resistance, duration of mechanical ventilation and duration of admission to NICU/hospital were not reported. Most of the domains for risk of bias were at low risk of bias for one study and at unclear risk of bias for the other study. The quality of the evidence using GRADE was low for neonatal sepsis, postpartum endometritis, and neonatal mortality and morbidity prior to discharge (Neonatal intensive care admissions) and of moderate quality for chorioamnionitis. AUTHORS' CONCLUSIONS: Current evidence indicates that compared to placebo, antibiotics for MSAF in labour may reduce chorioamnionitis. There was no evidence that antibiotics could reduce postpartum endometritis, neonatal sepsis and NICU admission. This systematic review identifies the need for more well-designed, adequately powered RCTs to assess the effect of prophylactic antibiotics in the incidence of maternal and neonatal complications.

E2 proteins of high risk human papillomaviruses down-modulate STING and IFN-κ transcription in keratinocytes.

In the early stages of human papillomavirus (HPV) infection, the viral proteins elicit specific immune responses that can participate to regression of ano-genital lesions. HPV E6 protein for instance can reduce type I interferon (IFN) including IFN-κ that is involved in immune evasion and HPV persistence. To evaluate the role of E2 protein in innate immunity in HPV16-associated cervical lesions, genome-wide expression profiling of human primary keratinocytes (HPK) transduced by HPV16 E2 was investigated using microarrays and innate immunity associated genes were specifically analyzed. The analyses showed that the expression of 779 genes was modulated by HPV16E2 and 92 of them were genes associated with innate immunity. Notably IFN-κ and STING were suppressed in HPK expressing the E2 proteins of HPV16 or HPV18 and the trans-activation amino-terminal domain of E2 was involved in the suppressive effect. The relationship between STING, IFN-κ and interferon stimulated genes (ISGs) in HPK was confirmed by gene silencing and real time PCR. The expression of STING and IFN-κ were further determined in clinical specimens by real time PCR. STING and IFN-κ were down-modulated in HPV positive low grade squamous intraepithelial lesions compared with HPV negative controls. This study demonstrates that E2 proteins of high risk HPV reduce STING and IFN-κ transcription and its downstream target genes that might be an immune evasion mechanism involved in HPV persistence and cervical cancer development.

Terbutaline pump maintenance therapy after threatened preterm labour for reducing adverse neonatal outcomes.

BACKGROUND: After successful inhibition of threatened preterm labour women are at high risk of recurrent preterm labour. Terbutaline pump maintenance therapy has been used to reduce adverse neonatal outcomes. This review replaces an earlier Cochrane review, published in 2002, which is no longer being updated by the team. OBJECTIVES: To determine the effectiveness of terbutaline pump maintenance therapy after threatened preterm labour in reducing adverse neonatal outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2014) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials comparing terbutaline pump therapy with alternative therapy, placebo, or no therapy after arrest of threatened preterm labour. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for inclusion and then extracted data as eligible for inclusion in qualitative and quantitative synthesis (meta-analysis). MAIN RESULTS: Four studies were included with a total of 234 women randomised. The overall methodological quality of the included studies was mixed; two studies provided very little information on study methods, there was high sample attrition in one study and in three studies the risk of performance bias was high. We found no strong evidence that terbutaline maintenance therapy offered any advantages over saline placebo or oral terbutaline maintenance therapy in reducing adverse neonatal outcomes by prolonging pregnancy among women with arrested preterm labour. The mean difference (MD) for gestational age at birth was -0.14 weeks (95% confidence interval (CI) -1.66 to 1.38) for terbutaline pump therapy compared with saline placebo pump for two trials combined. One trial reported a risk ratio (RR) of 1.17 (95% CI 0.79 to 1.73) for preterm birth (less than 37 completed weeks) and a RR of 0.97 (95% CI 0.51 to 1.84) of very preterm birth (less than 34 completed weeks) for terbutaline pump compared with saline placebo pump. We found no evidence that terbutaline pump therapy was associated with statistically significant reductions in infant respiratory distress syndrome, or neonatal intensive care unit admission compared with placebo. Compared with oral terbutaline, we found no evidence that pump therapy increased the rate of therapy continuation, or reduced the rate of infant complications or maternal hospital re-admissions. One study suggested that pump therapy resulted in significantly increased weekly cost/woman, $580 versus $12.50 (P < 0.01). No data were reported on long-term infant outcomes. AUTHORS' CONCLUSIONS: We found no evidence that terbutaline pump maintenance therapy decreased adverse neonatal outcomes. Taken together with the lack of evidence of benefit, its substantial expense and the lack of information on the safety of the therapy do not support its use in the management of arrested preterm labour. Future use should only be in the context of well-conducted, adequately powered randomised controlled trials.

Paracervical local anaesthesia for cervical dilatation and uterine intervention.

BACKGROUND: Cervical dilatation and uterine intervention can be performed under sedation, local or general anaesthesia for obstetrics and gynaecological conditions. Many gynaecologists use paracervical local anaesthesia but its effectiveness is unclear. This review was originally published in 2009 and was updated in 2013. OBJECTIVES: The objectives of this review were to determine the effectiveness and safety of paracervical local anaesthesia for cervical dilatation and uterine intervention, versus no treatment, placebo, other methods of regional anaesthesia, sedation and systemic analgesia, and general anaesthesia. SEARCH METHODS: We reran our search to August 2013. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 8), MEDLINE (1966 to August 2013), EMBASE (1980 to August 2013), and reference lists of articles. The original search was performed in January 2006. SELECTION CRITERIA: We included randomized or controlled clinical studies involving women who underwent cervical dilatation and uterine intervention for obstetrics and gynaecological conditions. We included studies which compared paracervical anaesthesia with no treatment, placebo, other methods of regional anaesthesia, systemic sedation and analgesia, or general anaesthesia. DATA COLLECTION AND ANALYSIS: Two authors independently evaluated the studies, extracted data, and checked and entered data into Review Manager. MAIN RESULTS: This updated review includes nine new studies, in total 26 studies with 28 comparisons and involving 2790 participants. No study of local paracervical versus general anaesthesia met our criteria. Ten studies compared local anaesthetic versus placebo. Paracervical local anaesthetic (PLA) reduced pain on cervical dilatation with a standardized mean difference (SMD) of 0.37 (95% CI 0.17 to 0.58) and a relative risk (RR) of severe pain of 0.16 (95% CI 0.06 to 0.74). PLA also reduced abdominal pain during, but not after, uterine intervention (SMD 0.74, 95% CI 0.28 to 1.19); there was no evidence of any effect on postoperative back or shoulder pain. Comparisons against no treatment did not demonstrate any effect of PLA. Five studies compared paracervical block with uterosacral block, intracervical block, or intrauterine topical anaesthesia. Two of these studies showed no significant difference in pain during the procedure. Compared to intrauterine instillation, PLA slightly reduced severe pain (from 8.3 to 7.6 on a 10-point scale), which may be negligible. Six studies compared PLA with sedation. There were no statistically significant differences in pain during or after the procedure, postoperative analgesia requirement, adverse effects, patient satisfaction, and the operator's perception of analgesia. We performed risk of bias assessment using six domains and found that more than half of the included studies had low risk of bias. AUTHORS' CONCLUSIONS: We found that no technique provided reliable pain control in the 26 included studies. Some studies reported that women experienced severe pain (mean scores of 7 to 9 out of 10) during uterine intervention, irrespective of the analgesic technique used. We concluded that the available evidence fails to show whether paracervical block is inferior, equivalent, or superior to alternative analgesic techniques in terms of efficacy and safety for women undergoing cervical dilatation and uterine interventions. We suggest that woman are likely to consider the rates and severity of pain during uterine interventions when performed awake to be unacceptable in the absence of neuraxial blockade, which are unaltered by paracervical block.