Dietary intake of pregnant women with non-alcoholic fatty liver disease: A case-control study.

BACKGROUND AND AIMS: Findings on the role of diet in non-alcoholic fatty liver disease (NAFLD) pathogenesis are inconsistent. There are few studies on the dietary habits of pregnant women with NAFLD. Our primary aim was to compare the dietary intakes of pregnant women with and without NAFLD. METHODS: This case-control study recruited 60 women (26-34 weeks' gestation) with recently diagnosed gestational diabetes (GDM) before any treatment was implemented. At recruitment, all participants underwent B-mode hepatic ultrasound. We included 30 women with sonographic NAFLD (cases) and 30 women without NAFLD (controls) matched for age, skin color, and pre-pregnancy body mass index. We assessed participants' dietary intakes in the last six months using a validated food frequency questionnaire. Mann-Whitney´s test was used to compare differences in median macro and micronutrient intakes between cases and controls. RESULTS: Total median daily energy (1965.1 × 1949.2 calories) and lipid (25.1% × 28.3%) intakes were similar in women with and without NAFLD and fell within recommended ranges. Participants with NAFLD reported significantly higher median daily intakes of carbohydrates (59.4% × 53.1% p = 0.003), and significantly lower protein (15.6% × 17.0% p = 0.005), fiber (10.7 × 13.3 g/day p = 0.010), and vitamin C (151.8 × 192.6 mg/day p = 0.008) intakes than those without NAFLD. CONCLUSIONS: Pregnant women with NAFLD ingest more carbohydrates and less protein, fiber, and vitamin C than those without NAFLD. Our findings contribute to understanding the role of diet in the development of NAFLD in pregnant women.

Pregnant women's experience of undergoing an oral glucose tolerance test: A cross-sectional study.

AIMS: The oral glucose tolerance test (OGTT) is routinely performed in most pregnancies; however, there are few studies which document the experience of taking this test. We assessed the experience of pregnant women during an OGTT. METHODS: This cross-sectional study included 152 women (24-32 weeks' gestation) and assessed their knowledge, anxiety (Spielberg anxiety inventory test-STAI), and physical pain (0-10 visual analog scale) during the OGTT. The Friedman test was used to compare pain scores over time. RESULTS: 61 (40%) participants did not know why they were doing the OGTT and 73 (48%) women had high state-anxiety levels (STAI ≥ 41 points, 20-80 scale). Participants had mild to moderate pain scores immediately after the first and second blood draws (3.9 ± 2.7 and 3.8 ± 2.3, respectively) that decreased significantly after the third blood draw (2.8 ± 2.4, P < 0.001). Nearly half (n = 71, 47%) of the participants were very or extremely bothered with having to drink the glucose solution. CONCLUSIONS: The OGTT was associated with high levels of anxiety and mild to moderate physical pain. Ingestion of the glucose solution was perceived as the most difficult part of the test. Good strategies can help to mitigate some of these negative experiences while undergoing an OGTT.

Analgesia during Labor and Vaginal Birth among Women with Severe Maternal Morbidity: Secondary Analysis from the WHO Multicountry Survey on Maternal and Newborn Health.

AIM: To evaluate the use of analgesia for vaginal birth, in women with and without severe maternal morbidity (SMM) and to describe sociodemographic, clinical, and obstetric characteristics and maternal and perinatal outcomes associated with labor analgesia. METHODS: Secondary analysis of the WHO Multicountry Survey on Maternal and Newborn Health (WHO-MCS), a global cross-sectional study performed between May 2010 and December 2011 in 29 countries. Women who delivered vaginally and had an SMM were included in this analysis and were then divided into two groups: those who received and those who did not receive analgesia for labor/delivery. We further compared maternal characteristics and maternal and perinatal outcomes between these two groups. RESULTS: From 314,623 women originally included in WHO-MCS, 9,788 developed SMM and delivered vaginally, 601 (6.1%) with analgesia and 9,187 (93.9%) without analgesia. Women with SMM were more likely to receive analgesia than those who did not experience SMM. Global distribution of SMM was similar; however, the use of analgesia was less prevalent in Africa. Higher maternal education, previous cesarean section, and nulliparity were factors associated with analgesia use. Analgesia was not an independent factor associated with an increase of severe maternal outcome (Maternal Near Miss + Maternal Death). CONCLUSIONS: The overall use of analgesia for vaginal delivery is low but women with SMM are more likely to receive analgesia during labor. Social conditions are closely linked with the likelihood of having analgesia during delivery and such a procedure is not associated with increased adverse maternal outcomes. Expanding the availability of analgesia in different levels of care should be a concern worldwide.

Systematic review and meta-analysis of studies on delivery preferences in Brazil.

BACKGROUND: Cesarean delivery rates in Brazil are among the highest in the world. User preference is often mentioned as an important factor driving this. OBJECTIVES: To identify, appraise, and synthesize the results of studies into delivery preferences in Brazil. SEARCH STRATEGY: MEDLINE, LILACS, and PsycINFO databases were searched, without language restrictions, using "delivery" and "preference" from inception to November 4, 2017. SELECTION CRITERIA: Cross-sectional or cohort studies with quantitative data on delivery preferences of lay persons in Brazil. DATA COLLECTION AND ANALYSIS: Two reviewers performed study selection, quality assessment, and data extraction. A meta-analysis of proportions with a preference for cesarean delivery was performed, including subgroups analyses. MAIN RESULTS: There were 28 studies with 31 071 participants included. The overall prevalence of preference for cesarean delivery was 27.2% (95% confidence interval [CI] 26.7%-27.7%; 28 studies, n=31 071). Cesarean delivery preference was higher among multiparas with previous cesarean deliveries (58.0%, 95% CI 56.6%-59.3%; nine studies, n=5542) than among multiparas without prior cesarean deliveries (17.3%, 95% CI 16.4%-18.2%; eight studies, n=7903), and among women with private health insurance (44.3%, 95% CI 43.0%-45.6%; nine studies, n=6048) than among those who depended on the public healthcare system (22.7%, 95% CI 22.2%-23.3%; 20 studies, n=24 314). CONCLUSIONS: Overall, most lay persons in Brazil did not prefer to deliver by cesarean.

Gestational tissue inflammatory biomarkers at term labor: A systematic review of literature.

Parturition at term is characterized by inflammatory overload in both feto-maternal tissues. Despite the large number of individual studies on changes in inflammatory biomarkers linked to labor, a comprehensive profile of them in each of the uterine compartments is not available to better understand their mechanistic contributions to labor. This systematic review investigated the pro- and anti-inflammatory biomarkers reported in intra-uterine tissues (amnion, chorion, decidua, placenta, and myometrium) at term labor. We conducted a systematic review of studies on pro- and anti-inflammatory biomarkers (mRNA and/or protein) reported in feto-maternal tissues during normal human term labor, published in English (1980-2016), in 3 electronic data bases. From a total of 3712 citations, 172 were included for final review. Each tissue expresses a unique set of biomarkers at the time of term labor, but there is significant overlap between tissues. All tissues had IL-6, IL-8, IL-1ß, COX-2, PGE-2, TNF-α, and hCAP18 in common at term labor. Common and unique inflammatory biomarkers are expressed in various feto-maternal compartments at term labor. Increase in pro-inflammatory markers in all gestational tissue signifies their harmonious functional role in promoting labor. Anti-inflammatory markers at term labor are hardly reported.

Increases in Caesarean Delivery Rates and Change of Perinatal Outcomes in Low- and Middle-Income Countries: A Hospital-Level Analysis of Two WHO Surveys.

BACKGROUND: Maternal and neonatal outcomes have improved substantially. During the same period, the caesarean delivery rate soared. The aim of this analysis was to determine whether an increase in caesarean rate was associated with an improvement in perinatal outcome at an institutional level in low- and middle-income countries. METHODS: The WHO Global Survey on Maternal and Perinatal Health (WHOGS) and the WHO Multi-Country Survey on Maternal and Newborn Health (WHOMCS) were two multi-country, facility-based, cross-sectional surveys conducted in 2004-08 and 2010-11, respectively. The increase in caesarean rate and the change of prevalence of adverse perinatal outcomes were calculated using a two-point estimator of percent change annualized (PCA) method. Maternal, perinatal, and neonatal composite indexes were used as the outcomes. A linear mixed model was used to assess the association between the change of caesarean rate and the change of perinatal outcome. RESULTS: A total of 259 facilities in 20 countries participated in both surveys, with 217 844 women in WHOGS and 227 734 women in WHOMCS. The caesarean rate in these facilities increased, on average, by 4.0% annually, while the prevalence of adverse perinatal outcomes decreased by 4.6% annually. However, after adjustments for potential confounders, no association was found between the increase in caesarean rate and the change of adverse outcome indexes, regardless of whether starting caesarean rates were already high (above 10%) or not. CONCLUSIONS: In low- and middle-income countries, the increases in caesarean rates were not associated with improved perinatal outcomes regardless of whether the starting caesarean rate was already high or not.

Contraceptive practices in women with sickle-cell disease.

This was a cross-sectional study of sexually active women with sickle-cell disease (SCD) managed at São Paulo Federal University during a one-year period. A total of 54 women were included. Mean age was 32.0 (11.2, standard deviation) years and almost 95% were black or of mixed racial ancestry. Almost 80% reported a history of multiple blood transfusions, 50% had kidney disease and 17% had a history of thrombosis. Over 80% of them had used some form of contraception, mostly combined hormonal contraceptive (52%) or progestin-only contraceptives (46%). Although most women had multiple comorbidities which would contraindicate the use of combined hormonal contraceptives, this was the most popular method used by them. We did not identify an association between the use of combined hormonal contraceptives and major complications. Larger, prospective studies are needed to evaluate the use and the effects of contraceptive methods in women with SCD.

Zinc supplementation for tinnitus.

BACKGROUND: Tinnitus is the perception of sound without external acoustic stimuli. Patients with severe tinnitus may have physical and psychological complaints and their tinnitus can cause deterioration in their quality of life. At present no specific therapy for tinnitus has been found to be satisfactory in all patients. In recent decades, a number of reports have suggested that oral zinc supplementation may be effective in the management of tinnitus. Since zinc has a role in cochlear physiology and in the synapses of the auditory system, there is a plausible mechanism of action for this treatment. OBJECTIVES: To evaluate the effectiveness and safety of oral zinc supplementation in the management of patients with tinnitus. SEARCH METHODS: The Cochrane ENT Information Specialist searched the ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2016, Issue 6); PubMed; EMBASE; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 14 July 2016. SELECTION CRITERIA: Randomised controlled trials comparing zinc supplementation versus placebo in adults (18 years and over) with tinnitus. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures recommended by Cochrane. Our primary outcome measures were improvement in tinnitus severity and disability, measured by a validated tinnitus-specific questionnaire, and adverse effects. Secondary outcomes were quality of life, change in socioeconomic impact associated with work, change in anxiety and depression disorders, change in psychoacoustic parameters, change in tinnitus loudness, change in overall severity of tinnitus and change in thresholds on pure tone audiometry. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics. MAIN RESULTS: We included three trials involving a total of 209 participants. The studies were at moderate to high risk of bias. All included studies had differences in participant selection criteria, length of follow-up and outcome measurement, precluding a meta-analysis. The participants were all adults over 18 years with subjective tinnitus, but one study conducted in 2013 (n = 109) included only elderly patients. Improvement in tinnitus severity and disabilityOnly the study in elderly patients used a validated instrument (Tinnitus Handicap Questionnaire) for this primary outcome. The authors of this cross-over study did not report the results of the two phases separately and found no significant differences in the proportion of patients reporting tinnitus improvement at four months of follow-up: 5% (5/93) versus 2% (2/94) in the zinc and placebo groups, respectively (risk ratio (RR) 2.53, 95% confidence interval (CI) 0.50 to 12.70; very low-quality evidence).None of the included studies reported any significant adverse effects. Secondary outcomesFor the secondary outcome change in tinnitus loudness, one study reported no significant difference between the zinc and placebo groups after eight weeks: mean difference in tinnitus loudness -9.71 dB (95% CI -25.53 to 6.11; very low-quality evidence). Another study also measured tinnitus loudness but used a 0- to 100-point scale. The authors of this second study reported no significant difference between the zinc and placebo groups after four months: mean difference in tinnitus loudness rating scores 0.50 (95% CI -5.08 to 6.08; very low-quality evidence).Two studies used unvalidated instruments to assess tinnitus severity. One (with 50 participants) reported the severity of tinnitus using a non-validated scale (0 to 7 points) and found no significant difference in subjective tinnitus scores between the zinc and placebo groups at the end of eight weeks of follow-up (mean difference (MD) -1.41, 95% CI -2.97 to 0.15; very low-quality evidence). A third trial (n = 50) also evaluated the improvement of tinnitus using a non-validated instrument (a 0 to 10 scale: 10 = severe and unbearable tinnitus). In this study, after eight weeks there was no difference in the proportion of patients with improvement in their tinnitus, 8.7% (2/23) treated with zinc versus 8% (2/25) of those who received a placebo (RR 1.09, 95% CI 0.17 to 7.10, very low-quality evidence).None of the included studies reported any of our other secondary outcomes (quality of life, change in socioeconomic impact associated with work, change in anxiety and depression disorders, change in psychoacoustic parameters or change in thresholds on pure tone audiometry). AUTHORS' CONCLUSIONS: We found no evidence that the use of oral zinc supplementation improves symptoms in adults with tinnitus.

Chewing gum for enhancing early recovery of bowel function after caesarean section.

BACKGROUND: Caesarean sections (CS) are the most frequent major surgery in the world. A transient impairment of bowel motility is expected after CS. Although this usually resolves spontaneously within a few days, it can cause considerable discomfort, require symptomatic medication and delay hospital discharge, thus increasing costs. Chewing gum in the immediate postoperative period is a simple intervention that may be effective in enhancing recovery of bowel function in other types of abdominal surgeries. OBJECTIVES: To assess the effects of chewing gum to reduce the duration of postoperative ileus and to enhance postoperative recovery after a CS. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (20 June 2016), LILACs (20 June 2016), ClinicalTrials.gov (20 June 2016), WHO International Clinical Trials Registry Platform (ICTRP) (20 June 2016) and the reference lists of retrieved studies. SELECTION CRITERIA: All randomised controlled trials comparing chewing gum versus usual care, for women in the first 24 hours after a CS. We included studies published in abstract form only.Quasi-randomised, cross-over or cluster-randomised trials were not eligible for inclusion in this review. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the studies for inclusion, extracted data and assessed the risk of bias following standard Cochrane methods. We present dichotomous outcome results as risk ratio (RR) with 95% confidence intervals (CI) and continuous outcome results as mean differences (MD) and 95% CI. We pooled the results of similar studies using a random-effects model in case of important heterogeneity. We used the GRADE approach to assess the overall quality of evidence. MAIN RESULTS: We included 17 randomised trials (3149 participants) conducted in nine different countries. Seven studies (1325 women) recruited exclusively women undergoing elective CS and five studies (833 women) only included women having a primary CS. Ten studies (1731 women) used conventional feeding protocols (nil by mouth until the return of intestinal function). The gum-chewing regimen varied among studies, in relation to its initiation (immediately after CS, up to 12 hours later), duration of each session (from 15 to 60 minutes) and number of sessions per day (three to more than six). All the studies were classified as having a high risk of bias due to the nature of the intervention, women could not be blinded and most of the outcomes were self-reported.Primary outcomes of this review: for the women that chewed gum, the time to passage of first flatus was seven hours shorter than those women in the 'usual care' control group (MD -7.09 hours, 95% CI -9.27 to -4.91 hours; 2399 women; 13 studies; random-effects Tau² = 14.63, I² = 95%, very low-quality evidence). This effect was consistent in all subgroup analyses (primary and repeat CS, time spent chewing gum per day, early and conventional feeding protocols, elective and non-elective CS and time after CS when gum-chewing was initiated). The rate of ileus was on average over 60% lower in the chewing-gum group compared to the control (RR 0.39, 95% CI 0.19 to 0.80; 1139 participants; four studies; I² = 39%, low-quality evidence). Tolerance to gum-chewing appeared to be high. Three women in one study complained about the chewing gum (but no further information was provided) and none of the studies reported adverse effects (eight studies, 925 women, low-quality evidence).Secondary outcomes of this review: the time to passage of faeces occurred on average nine hours earlier in the intervention group (MD -9.22 hours, 95% CI -11.49 to -6.95 hours; 2016 participants; 11 studies; random-effects Tau² = 12.53, I² = 93%, very low-quality evidence). The average duration of hospital stay was shorter in the intervention compared to the control group (MD -0.36 days, 95% CI -0.53 to -0.18 days; 1489 participants; seven studies; random-effects Tau² = 0.04, I² = 92%). The first intestinal sounds were heard earlier in the intervention than in the control group (MD -4.56 hours, 95% CI -6.18 to -2.93 hours; 1729 participants; nine studies; random-effects Tau² = 5.41, I² = 96%). None of the studies assessed women's satisfaction in relation to having to chew gum. The need for analgesia or antiemetic agents did not differ between the intervention and control groups (average RR 0.50, 95% CI 0.12 to 2.13; 726 participants; three studies; random-effects Tau² = 0.79, I² = 69%). AUTHORS' CONCLUSIONS: This review found 17 randomised controlled trials (involving 3149 women). We downgraded the quality of the evidence for time to first passage of flatus and of faeces and for adverse effects/intolerance to gum chewing because of the high risk of bias of the studies (due to lack of blinding and self-report). For time to first flatus and faeces, we downgraded the quality of the evidence further because of the high heterogeneity in these meta-analyses and the potential for publication bias based on the visual inspection of the funnel plots. The quality of the evidence for adverse effects/tolerance to gum chewing and for ileus was downgraded because of the small number of events. The quality of the evidence for ileus was further downgraded due to the unclear risk of bias for the assessors evaluating this outcome.The available evidence suggests that gum chewing in the immediate postoperative period after a CS is a well tolerated intervention that enhances early recovery of bowel function. However the overall quality of the evidence is very low to low.Further research is necessary to establish the optimal regimen of gum-chewing (initiation, number and duration of sessions per day) to enhance bowel function recovery and to assess potential adverse effects of and women's satisfaction with this intervention. New studies also need to assess the compliance of the participants to the recommended gum-chewing instructions. Future large, well designed and conducted studies, with better methodological and reporting quality, will help to inform future updates of this review and enhance the body of evidence for this intervention.

Bioidentical hormones for women with vasomotor symptoms.

BACKGROUND: Various hormone therapies (HT) are available to treat menopausal vasomotor symptoms. Bioidentical hormones are chemically identical to those produced by the human body, and several types are well-tested and available on prescription. Many women have opted for bioidentical hormone therapy (BHT) on the assumption that it is safer than other forms of HT. We evaluated the evidence. OBJECTIVES: To determine the effectiveness and safety of bioidentical hormones compared to placebo or non-bioidentical hormones for the relief of vasomotor symptoms. SEARCH METHODS: In July 2015 we searched the Cochrane Central Register of Controlled Trials, PubMed, Embase, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), registers of ongoing trials and the reference lists of articles retrieved. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing bioidentical hormone therapy (BHT) versus placebo or non-bioidentical hormones. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by the Cochrane Collaboration. Our primary outcome was vasomotor symptoms (hot flushes and night sweats). We evaluated the overall quality of the evidence using Grading of Recommendations Assessment, Development and Evaluation criteria (GRADE). MAIN RESULTS: We included 23 RCTs (5779 participants). Most studies (20/23) included only women with moderate to severe hot flushes. All studies compared unopposed 17 beta-estradiol (beta-estradiol) versus placebo or conjugated equine estrogens (CEE). None of the studies reported night sweats as a separate outcome. BHT patch versus placebo Frequency of hot flushesFour RCTs reported data suitable for analysis. There were fewer hot flushes in the BHT group, with a moderate to large effect size (SMD -0.68, 95% CI -0.83 to -0.53, four RCTs, 793 women, I(2) = 67%, low quality evidence). There was moderate heterogeneity, but a consistent direction of effect. Seven RCTs reported data unsuitable for analysis; all reported a benefit in the intervention group. Symptom intensityTwo RCTs reported analysable data. Measured on a 0-100 visual analogue scale (VAS), hot flush intensity was lower in the BHT group (MD -19.94 points, 95% CI -24.86 to -15.02, two RCTs, 393 women, I(2) = 54%, low quality evidence). There was moderate heterogeneity, but a consistent direction of effect. Adverse effectsAdverse events (such as headache, vaginal bleeding, breast tenderness and skin reactions) were more common in the intervention group (odds ratio (OR) 2.14, 95% CI 1.29 to 3.54, 9 RCTs, 1822 women, I(2) = 73%, low quality evidence). There was moderate heterogeneity, but a consistent direction of effect. In one study, five women in the intervention group developed endometrial hyperplasia. BHT gel versus placebo Hot flush frequencyThree RCTs reported this outcome, but the data were unsuitable for analysis. All reported a benefit in the BHT group. Adverse effectsAdverse events were more common in the BHT group (OR 1.41, 95% CI 1.09 to 1.83, 3 RCTs, 1086 women, I(2) = 0%, moderate quality evidence). Oral BHT versus placebo Hot flush frequencyTwo studies reported analysable data. There were fewer hot flushes in the BHT group, with a moderate to large effect size (SMD -0.80, 95% CI -1.03 to -0.57, two RCTs, 356 women, I(2) = 14%, low quality evidence). Adverse effectsThere was no evidence of a difference between the groups (OR 1.28, 95% CI 0.84 to 1.96, 3 RCTs, 433 women, I(2) = 0%, low quality evidence). Topical BHT emulsion versus placebo Hot flush frequencyOne study with data unsuitable for analysis reported a benefit in the intervention group. Adverse effectsThere was no evidence of a difference between the groups (OR 1.46, 95% CI 0.80 to 2.66, one RCT, 200 women, low quality evidence). Intranasal BHT versus placebo Hot flush frequencyOnly one study reported analysable data. There were fewer hot flushes per day in the BHT group (MD -3.04 95% CI -4.05 to -2.03, one study, 458 women, moderate quality evidence) Adverse effectsAdverse events (such as headache, breast tenderness, arthralgia and nausea) were more common in the intervention group (OR 1.96, 95% CI 1.26 to 3.03, one RCT, 458 women, moderate quality evidence). Subgroup analysesSubgroup analyses by dose of BHT suggested that higher doses of BHT may be associated with more effectiveness but also higher risk of adverse effects. BHT patch versus 0.625 mg CEETwo RCTs reported this comparison, but the data were unsuitable for analysis. Hot flush frequencyBoth RCTs reported no evidence of a difference between the groups. Adverse effectsFindings were inconsistent. In one comparison (0.1 mg BHT versus CEE), breast pain and vaginal bleeding were more frequent in the BHT group. Oral BHT versus 0.625 mg CEE Hot flush frequencyOne study with data unsuitable for analysis reported no evidence of a difference between the groups. Adverse effectsThere was no evidence of a difference between the groups (OR 1.20, 95% CI 0.50 to 2.87, one RCT, 103 women, very low quality evidence). AUTHORS' CONCLUSIONS: There was low to moderate quality evidence that BHT in various forms and doses is more effective than placebo for treating moderate to severe menopausal hot flushes. There was low to moderate quality evidence of higher rates of adverse effects such as headache, vaginal bleeding, breast tenderness and skin reactions in the BHT group. There was some evidence to suggest that higher doses of BHT are associated with greater effectiveness but also with higher risk of adverse effects. Although all the included studies used unopposed estrogen, it is recommended best practice to use progestogen therapy in women with a uterus taking estrogen in order to avoid endometrial hyperplasia, regardless of the source of the estrogen. No data are yet available about the safety of BHT with regard to long-term outcomes such as heart attack, stroke and breast cancer.There was no good evidence of a difference in effectiveness between BHT and CEE, and findings with regard to adverse effects were inconsistent. The quality of the evidence was too low to reach any firm conclusions.The main limitations in the quality of the evidence were study risk of bias (mainly due to poor reporting of methods), imprecision and lack of data suitable for analysis.

Polyunsaturated fatty acid supplementation for drug-resistant epilepsy.

BACKGROUND: An estimated 1% to 3% of all individuals will receive a diagnosis of epilepsy during their lives, which corresponds to approximately 50 million affected people worldwide. The real prevalence is possibly higher because epilepsy is underreported in developing countries. Although most will achieve adequate control of their disease though the use of medication, approximately 25% to 30% of all those with epilepsy are refractory to pharmacological treatment and will continue to have seizures despite the use of two or more agents in adequate dosages. Over the last decade, researchers have tested the use of polyunsaturated fatty acid (PUFA) supplements for the treatment of refractory epilepsy, with inconsistent results. There have also been some concerns about the use of omega-3 PUFA compounds because they reduce platelet aggregation and could, in theory, cause bleeding. OBJECTIVES: To assess the effectiveness and tolerability of omega-3 polyunsaturated fatty acids (eicosapentaenoic acid-EPA and docosahexanoic acid-DHA) in the control of seizures in people with refractory epilepsy. SEARCH METHODS: We searched the Cochrane Epilepsy Group Specialised Register (from inception up to November 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, issue 11), MEDLINE (1948 to November 2015), EMBASE (1980 to November 2015), SCOPUS (1823 to November 2015); LILACS (Literatura Latino-Americana e do Caribe de Informação em Ciências da Saúde) (1982 to November 2015); ClinicalTrials.gov; World Health Organization (WHO) International Clinical Trials Registry Platform (November 2015). No language restrictions were imposed. We contacted study authors for additional and unpublished information and screened the reference lists of retrieved citations for potentially eligible studies not identified through the electronic search. SELECTION CRITERIA: All randomised and quasi-randomised studies using PUFAs for the treatment of drug-resistant epilepsy. DATA COLLECTION AND ANALYSIS: Two review authors were involved in study selection, data extraction and quality assessment of the included trials. The following outcomes were assessed: seizure freedom, seizure reduction, improvement in quality of life, potential adverse effects, gastrointestinal effects, drop-out rates and changes in plasma lipid profile. Primary analyses were by intention to treat. MAIN RESULTS: Eight studies were identified as potentially relevant; three fulfilled the selection criteria and were included in the review. Two placebo-controlled, double blind trials involving adult participants were conducted in developed countries, while one placebo-controlled, single blind trial involving children was conducted in a developing country (Egypt). Bromfield 2008 randomised 27 American adults to receive 2.2 g/day of omega-3 PUFAs (EPA:DHA in a 3:2 ratio) or placebo. Yuen 2005 randomised 58 people in the UK to approximately 1.7 g/day omega-3 PUFAs (1g EPA and 0.7g DHA) or placebo. Reda 2015 randomised 70 Egyptian children to receive 3 ml/day of 1200 mg fish oil (providing 0.24 g DHA and 0.36 g EPA) or placebo. The three studies recruited a total of 155 subjects (85 adults and 70 children); 78 of them (43 adults and 35 children) were randomised to PUFAs and 77 (42 adults and 35 children) to placebo. All participants were followed for up to 12 weeks. Seizure freedom was reported by only one study, with a high risk of bias, involving exclusively children. The risk estimate for this outcome was significantly higher in the children receiving PUFA compared to the control group (risk ratio (RR) 20.00, 95% confidence interval (CI) 2.84 to 140.99, 1 study, 70 children). Similarly, PUFA supplementation was associated with a significant difference in the proportion of children with at least 50% reduction in seizure frequency (RR 33.00 95% CI 4.77 to 228.15, 1 study with a high risk of bias, 70 children). However, this effect was not observed when the data from two studies including adult participants were pooled (RR 0.57, 95% CI 0.19 to 1.75, I² 0%, 2 studies, 78 participants, low-quality evidence). One of our three primary outcomes (adverse effects related to bleeding) was not assessed in any of the studies included in this review. There were no significant differences between the PUFA and control groups in relation to gastrointestinal effects (RR 0.78, 95% CI 0.32 to 1.89, 2 studies, 85 participants, low-quality evidence).Supplementation with PUFA did not produce significant differences in mean frequency of seizures, quality of life or other side effects. AUTHORS' CONCLUSIONS: In view of the limited number of studies and small sample sizes, there is not enough evidence to support the use of PUFA supplementation in people with refractory epilepsy. More trials are needed to assess the benefits of PUFA supplementation in the treatment of drug-resistant epilepsy.

Alemtuzumab for multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune, T-cell-dependent, inflammatory, demyelinating disease of the central nervous system, with an unpredictable course. Current MS therapies focus on treating exacerbations, preventing new exacerbations and avoiding the progression of disability. However, at present there is no effective treatment that is capable of safely and effectively reaching these objectives. This has led to the development and investigation of new drugs. Recent clinical trials suggest that alemtuzumab, a humanised monoclonal antibody against cell surface CD52, could be a promising option for MS. OBJECTIVES: To assess the safety and effectiveness of alemtuzumab used alone or associated with other treatments to decrease disease activity in patients with any form of MS. SEARCH METHODS: We searched the Trials Register of the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Group (30 April 2015), which contains trials from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, LILACS and the trial registry databases ClinicalTrials.gov and WHO International Clinical Trials Registry Platform. There was no restriction on the source, publication date or language. SELECTION CRITERIA: All randomised clinical trials (RCTs) involving adults diagnosed with any form of MS according to the McDonald criteria, comparing alemtuzumab alone or associated with other medications, at any dose and for any duration, versus placebo or any other active drug therapy or alemtuzumab in other dose, regimen or duration. The co-primary outcomes were relapse-free survival, sustained disease progression and number of participants with at least one of any adverse events, including serious adverse events. DATA COLLECTION AND ANALYSIS: Two independent review authors performed study selection, data extraction and 'Risk of bias' assessment. A third review author checked the process for accuracy. We used the Cochrane 'Risk of bias' tool to assess the risk of bias of the studies included in the review. We used the GRADE system to assess the quality of the body of evidence. To measure the treatment effect on dichotomous outcomes we used the risk ratio (RR); for the treatment effect on continuous outcomes, we used the mean difference (MD) and for time-to-event outcomes we used hazard ratio (HR). We calculated 95% confidence intervals (CI) for these measures. When there was no heterogeneity, we used a fixed-effect model to pool data. MAIN RESULTS: Three RCTs (1713 participants) fulfilled the selection criteria and we included them in the review. All three trials compared alemtuzumab versus subcutaneous interferon beta-1a for patients with relapsing-remitting MS. Patients were treatment-naive in the CARE-MS and CAMMS223 studies. The CARE-MS II study included patients with at least one relapse while being treated with interferon beta or glatiramer acetate. Alemtuzumab was given for 12 or 24 months; for some outcomes, the follow-up period reached 36 months. The regimens were (a) 12 mg or 24 mg per day administered intravenously, once a day for five consecutive days at month 0 and 12 or (b) 24 mg per day, intravenously, once a day for three consecutive days at month 12 and 24. The patients in the other arm of the trials received interferon beta-1a 44 µg subcutaneously three times weekly after dose titration.At 24 months, alemtuzumab 12 mg was associated with: (a) higher relapse-free survival (hazard ratio (HR) 0.50, 95% CI 0.41 to 0.60; 1248 participants, two studies, moderate quality evidence); (b) higher sustained disease progression-free survival (HR 0.62, 95% CI 0.44 to 0.87; 1191 participants; two studies; moderate quality evidence); (c) a slightly higher number of participants with at least one adverse event (RR 1.04, 95% CI 1.01 to 1.06; 1248 participants; two studies; moderate quality evidence); (d) a lower number of participants with new or enlarging T2-hyperintense lesions on magnetic resonance imaging (MRI) (RR 0.74, 95% CI 0.59 to 0.91; 1238 participants; two studies; I(2) = 80%); and (e) a lower number of dropouts (RR 0.31, 95% CI 0.23 to 0.41; 1248 participants; two studies, I(2) = 29%; low quality evidence).At 36 months, alemtuzumab 24 mg was associated with: (a) higher relapse-free survival (45 versus 17; HR 0.21, 95% CI 0.11 to 0.40; one study; 221 participants); (b) a higher sustained disease progression-free survival (HR 0.33, 95% CI 0.16 to 0.69; one study; 221 participants); and (c) no statistical difference in the rate of participants with at least one adverse event. We did not find any study that reported any of the following outcomes: rate of participants free of clinical disease activity, quality of life, fatigue or change in the numbers of MRI T2- and T1-weighted lesions after treatment. It was not possible to perform subgroup analyses according to disease type and disability at baseline due to lack of data. AUTHORS' CONCLUSIONS: In patients with relapsing-remitting MS, alemtuzumab 12 mg was better than subcutaneous interferon beta-1a for the following outcomes assessed at 24 months: relapse-free survival, sustained disease progression-free survival, number of participants with at least one adverse event and number of participants with new or enlarging T2-hyperintense lesions on MRI. The quality of the evidence for these results was low to moderate. Alemtuzumab 24 mg seemed to be better than subcutaneous interferon beta-1a for relapse-free survival and sustained disease progression-free survival, at 36 months.More randomised clinical trials are needed to evaluate the effects of alemtuzumab on other forms of MS and compared with other therapeutic options. These new studies should assess additional relevant outcomes such as the rate of participants free of clinical disease activity, quality of life, fatigue and adverse events (individual rates, serious adverse events and long-term adverse events). Moreover, these new studies should evaluate other doses and durations of alemtuzumab course.

Infraorbital nerve block for postoperative pain following cleft lip repair in children.

BACKGROUND: Postoperative pain is a barrier to the quality of paediatric care, the proper management of which is a challenge. Acute postoperative pain often leads to adverse functional and organic consequences that may compromise surgical outcome. Cleft lip is one of the most common craniofacial birth defects and requires surgical correction early in life. As expected after a surgical intervention in such a sensitive and delicate area, the immediate postoperative period of cleft lip repair may be associated with moderate to severe pain. Infraorbital nerve block associated with general anaesthesia has been used to reduce postoperative pain after cleft lip repair. OBJECTIVES: To assess the effects of infraorbital nerve block for postoperative pain following cleft lip repair in children. SEARCH METHODS: We searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library, Issue 6, 2015), MEDLINE, EMBASE, and Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) from inception to 17 June 2015. There were no language restrictions. We searched for ongoing trials in the following platforms: the metaRegister of Controlled Trials; ClinicalTrials.gov (the US National Institutes of Health Ongoing Trials Register), and the World Health Organization International Clinical Trials Registry Platform (on 17 June 2015). We checked reference lists of the included studies to identify any additional studies. We contacted specialists in the field and authors of the included trials for unpublished data. SELECTION CRITERIA: We included randomised controlled clinical trials that tested perioperative infraorbital nerve block for cleft lip repair in children, compared with other types of analgesia procedure, no intervention, or placebo (sham nerve block). We considered the type of drug, dosage, and route of administration used in each study. For the purposes of this review, the term 'perioperative' refers to the three phases of surgery, that is preoperative, intraoperative, and postoperative, and commonly includes ward admission, anaesthesia, surgery, and recovery. DATA COLLECTION AND ANALYSIS: Two review authors (GF and EH) independently identified, screened, and selected the studies, assessed trial quality, and performed data extraction using the Cochrane Pain, Palliative and Supportive Care Review Group criteria. In case of disagreements, a third review author (EMKS) was consulted. We assessed the evidence using Grading of Recommendations, Assessment, Development and Evaluation (GRADE). MAIN RESULTS: We included eight studies involving 353 children in the review. These studies reported different types of interventions (lignocaine or bupivacaine), observation times, and forms of measuring and describing the outcomes, making it difficult to conduct meta-analyses. In the comparison of infraorbital nerve block versus placebo, there was a large effect in mean postoperative pain scores (our first primary outcome) favouring the intervention group (standardised mean difference (SMD) -3.54, 95% confidence interval (CI) -6.13 to -0.95; very low-quality evidence; 3 studies; 120 children). Only one study reported the duration of analgesia (in hours) (second primary outcome) with a difference favouring the intervention group (mean difference (MD) 8.26 hours, 95% CI 5.41 to 11.11; very low-quality evidence) and less supplemental analgesic requirements in the intervention group (risk ratio (RR) 0.05, 95% CI 0.01 to 0.18; low-quality evidence). In the comparison of infraorbital nerve block versus intravenous analgesia, there was a difference favouring the intervention group in mean postoperative pain scores (SMD -1.50, 95% CI -2.40 to -0.60; very low-quality evidence; 2 studies; 107 children) and in the time to feeding (MD -9.45 minutes, 95% CI -17.37 to -1.53; moderate-quality evidence; 2 studies; 128 children). No significant adverse events (third primary outcome) were associated with the intervention, although three studies did not report this outcome. Five out of eight studies found no unwanted side effects after the nerve blocks. Overall, the included studies were at low or unclear risk of bias. The reasons for downgrading the quality of the evidence using GRADE related to the lack of information about randomisation methods and allocation concealment in the studies, very small sample sizes, and heterogeneity of outcome reporting. AUTHORS' CONCLUSIONS: There is low- to very low-quality evidence that infraorbital nerve block with lignocaine or bupivacaine may reduce postoperative pain more than placebo and intravenous analgesia in children undergoing cleft lip repair. Further studies with larger samples are needed. Future studies should standardise the observation time and the instruments used to measure outcomes, and stratify children by age group.

Vaccines for preventing herpes zoster in older adults.

BACKGROUND: Herpes zoster, also known as 'shingles', is a neurocutaneous disease characterised by the reactivation of the latent varicella zoster virus (VZV), the virus that causes chickenpox when immunity to VZV declines. It is an extremely painful condition that can last many weeks or months and it can significantly compromise the quality of life of affected individuals. The natural process of aging is associated with a reduction in cellular immunity and this predisposes older people to herpes zoster. Vaccination with an attenuated form of VZV activates specific T cell production avoiding viral reactivation. The Food and Drug Administration has approved a herpes zoster vaccine with an attenuated active virus for clinical use among older adults, which has been tested in large populations. A new adjuvanted recombinant VZV subunit zoster vaccine has also been tested. It consists of recombinant VZV glycoprotein E and a liposome-based AS01B adjuvant system. This new vaccine is not yet available for clinical use. OBJECTIVES: To evaluate the effectiveness and safety of vaccination for preventing herpes zoster in older adults. SEARCH METHODS: For this 2015 update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 9), MEDLINE (1948 to the 3rd week of October 2015), EMBASE (2010 to October 2015), CINAHL (1981 to October 2015) and LILACS (1982 to October 2015). SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing zoster vaccine with placebo or no vaccine, to prevent herpes zoster in older adults (mean age > 60 years). DATA COLLECTION AND ANALYSIS: Two review authors independently collected and analysed data using a data extraction form. They also performed 'Risk of bias' assessment. MAIN RESULTS: We identified 13 studies involving 69,916 participants. The largest study included 38,546 participants. All studies were conducted in high-income countries and included only healthy Caucasian individuals ≥ 60 years of age without immunosuppressive comorbidities. Ten studies used live attenuated varicella zoster virus (VZV) vaccines. Three studies tested a new type of vaccine not yet available for clinical use. We judged five of the included studies to be at low risk of bias.The incidence of herpes zoster, at up to three years of follow-up, was lower in participants who received the vaccine than in those who received a placebo: risk ratio (RR) 0.49; 95% confidence interval (CI) 0.43 to 0.56, risk difference (RD) 2%, number needed to treat to benefit (NNTB) 50; GRADE: moderate quality evidence. The vaccinated group had a higher incidence of mild to moderate intensity adverse events. These date came from one large study that included 38,546 people aged 60 years or older.A study including 8122 participants compared the new vaccine (not yet available) to the placebo; the group that received the new vaccine had a lower incidence of herpes zoster at 3.2 years of follow-up: RR 0.04, 95% CI 0.02 to 0.10, RD 3%, NNTB 33; GRADE: moderate quality evidence. The vaccinated group had a higher incidence of adverse events but most them were of mild to moderate intensity.All studies received funding from the pharmaceutical industry. AUTHORS' CONCLUSIONS: Herpes zoster vaccine is effective in preventing herpes zoster disease and this protection can last three years. In general, zoster vaccine is well tolerated; it produces few systemic adverse events and injection site adverse events of mild to moderate intensity.There are studies of a new vaccine (with a VZV glycoproteic fraction plus adjuvant), which is currently not yet available for clinical use.

Maternal overweight and sexual function in pregnancy.

INTRODUCTION: Obesity and overweight are increasing worldwide and may compromise female sexual function. Our aim was to compare the sexual function of normal and overweight women in pregnancy. MATERIAL AND METHODS: A cross-sectional study involving 223 pregnant women: 105 overweight [pre-pregnancy body mass index (BMI) ≥ 25.0 kg/m(2) ] and 118 normal weight (BMI 18.5-24.9 kg/m(2) ), in the 2nd and 3rd trimester of pregnancy. These women were managed at an antenatal clinic of a public university hospital in São Paulo, Brazil, between 2011 and 2014. The Female Sexual Function Index (FSFI) was used. The characteristics of normal and overweight women were compared using two-tailed Student's t- or chi-squared tests. Differences in mean FSFI scores were assessed using the Kruskal-Wallis test. Pearson's correlation coefficient was used to assess the correlation between pre-pregnancy BMI and FSFI scores. RESULTS: In the 2nd trimester, mean total FSFI scores were similar in overweight (n = 51) compared to normal weight (n = 67) women (21.9 ± 9.8 vs. 21.7 ± 10.4, p = 1.000). In the 3rd trimester, overweight women (n = 54) had significantly lower total FSFI scores than normal weight women (n = 51; 19.1 ± 10.3 vs. 24.5 ± 9.7, p = 0.0004). In the 3rd trimester, overweight women also had significantly lower mean scores in desire, arousal, lubrication, orgasm and dyspareunia domains. We found an inverse correlation between pre-pregnancy BMI and mean 3rd trimester total FSFI scores (r = -0.212, p = 0.030), desire (r = -0.216, p = 0.027) and orgasm (r = -0.222, p = 0.023). CONCLUSION: Overweight women in the 3rd trimester of pregnancy had poorer sexual function compared with normal weight women.

Pharmacotherapy for sleep bruxism.

BACKGROUND: Sleep bruxism is an oral activity characterized by involuntary teeth grinding or clenching during sleep. Several forms of treatment have been proposed for this disorder, including behavioural, dental and pharmacological strategies. OBJECTIVES: To evaluate the effectiveness and safety of pharmacological therapy for the treatment of sleep bruxism compared with other drugs, no treatment or placebo. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 8, 2014), MEDLINE (1966 to August 2014), EMBASE (1980 to August 2013) and LILACS (1982 to August 2014). We identified additional reports from the reference lists of retrieved reports and from reviews on treatment of sleep bruxism. We applied no language restrictions. SELECTION CRITERIA: We selected randomized controlled trials (RCTs) or quasi-RCTs that compared drugs with other drugs, no treatment or placebo in people with sleep bruxism. DATA COLLECTION AND ANALYSIS: Review authors carried out data extraction and quality assessment of the included trials independently and in duplicate. We discussed discrepancies until we reached consensus. We consulted a third review author in cases of persistent disagreement. We contacted authors of primary studies when necessary. MAIN RESULTS: We identified 18 potentially relevant RCTs, but only seven met the inclusion criteria. All studies had a small number of participants, ranging from seven to 16 people per study and had a cross-over design. Three studies were of low risk of bias, while four were of uncertain risk. Amitriptyline (three studies), bromocriptine (one study), clonidine (one study), propranolol (one study), levodopa (Prolopa®) (one study) and tryptophan (one study) were compared with placebo. Studies evaluating bromocriptine, clonidine, propranolol and levodopa reported our primary outcome of indices of bruxism motor activity.Results were imprecise and consistent with benefit, no difference or harm. These were the specific findings for each of the drugs according to specific outcomes: 1. Amitriptyline versus placebo for masseteric electromyography (EMG) activity per minute: standardized mean difference (SMD) -0.28 (95% confidence interval (CI) -0.91 to 0.34; P value = 0.37), 2. bromocriptine versus placebo for bruxism episodes per hour: mean difference (MD) 0.60 (95% CI -2.93 to 4.13), bruxism bursts per hour: MD -2.00 (95% CI -53.47 to 49.47), bruxism bursts per episode: MD 0.50 (95% CI -1.85 to 2.85) or number of episodes with grinding noise: MD 2.40 (95% CI -24.00 to 28.80), 3. clonidine versus placebo for number of bruxism episodes per hour: MD -2.41 (95% CI -4.84 to 0.02), 4. propranolol versus placebo for the number of bruxism episodes per hour: MD 1.16 (95% CI -1.89 to 4.21), 5. L-tryptophan versus placebo for masseteric EMG activity per second: SMD 0.08 (95% CI -0.90 to 1.06) and 6. levodopa versus placebo for bruxism episodes per hour of sleep: MD -1.47 (95% CI -3.64 to 0.70), for bruxism bursts per episode: MD 0.06 (95% CI -2.47 to 2.59).We combined several secondary outcomes (sleep duration, masseteric EMG activity per minute and pain intensity) in a meta-analysis for comparison of amitriptyline with placebo. The results for most comparisons were uncertain because of statistical imprecision. One study reported that clonidine reduced rapid eye movement (REM) sleep stage and increased the second stage of sleep. However, results for other sleep-related outcomes with clonidine were uncertain. Adverse effects were frequent in people who took amitriptyline (5/10 had drowsiness, difficulty awakening in the morning, insomnia or xerostomia compared with 0/10 in the placebo group), as well as in people who received propranolol (7/16 had moderate-to-severe xerostomia compare with 2/16 in the placebo group). Clonidine was associated with prolonged morning hypotension in three of 16 participants. The use of preventive medication avoided any adverse effects in people treated with levodopa and bromocriptine. AUTHORS' CONCLUSIONS: There was insufficient evidence on the effectiveness of pharmacotherapy for the treatment of sleep bruxism. This systematic review points to the need for more, well-designed, RCTs with larger sample sizes and adequate methods of allocation, outcome assessment and duration of follow-up. Ideally, parallel RCTs should be used in future studies to avoid the bias associated with cross-over studies. There is a need to standardize the outcomes of RCTs on treatments for sleep bruxism.

Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems.

BACKGROUND: Pre-eclampsia and eclampsia are common causes of serious morbidity and death. Calcium supplementation may reduce the risk of pre-eclampsia, and may help to prevent preterm birth. OBJECTIVES: To assess the effects of calcium supplementation during pregnancy on hypertensive disorders of pregnancy and related maternal and child outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 March 2013) and contacted study authors for more data where possible. We updated the search in May 2014 and added the results to the 'Awaiting Classification' section of the review. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing high-dose (at least 1 g daily of calcium) or low-dose calcium supplementation during pregnancy with placebo or no calcium. DATA COLLECTION AND ANALYSIS: We assessed eligibility and trial quality, extracted and double-entered data. MAIN RESULTS: High-dose calcium supplementation (≥1 g/day)We included 14 studies in the review, however one study contributed no data. We included 13 high-quality studies in our meta-analyses (15,730 women). The average risk of high blood pressure (BP) was reduced with calcium supplementation compared with placebo (12 trials, 15,470 women: risk ratio (RR) 0.65, 95% confidence interval (CI) 0.53 to 0.81; I² = 74%). There was also a significant reduction in the risk of pre-eclampsia associated with calcium supplementation (13 trials, 15,730 women: RR 0.45, 95% CI 0.31 to 0.65; I² = 70%). The effect was greatest for women with low calcium diets (eight trials, 10,678 women: average RR 0.36, 95% CI 0.20 to 0.65; I² = 76%) and women at high risk of pre-eclampsia (five trials, 587 women: average RR 0.22, 95% CI 0.12 to 0.42; I² = 0%). These data should be interpreted with caution because of the possibility of small-study effect or publication bias.The composite outcome maternal death or serious morbidity was reduced (four trials, 9732 women; RR 0.80, 95% CI 0.65 to 0.97; I² = 0%). Maternal deaths were not significantly different (one trial of 8312 women: calcium group one death versus placebo group six deaths). There was an anomalous increase in the risk of HELLP (haemolysis, elevated liver enzymes and low platelets) syndrome (two trials, 12,901 women: RR 2.67, 95% CI 1.05 to 6.82; I² = 0%) in the calcium group, however, the absolute number of events was low (16 versus six).The average risk of preterm birth was reduced in the calcium group (11 trials, 15,275 women: RR 0.76, 95% CI 0.60 to 0.97; I² = 60%) and amongst women at high risk of developing pre-eclampsia (four trials, 568 women: average RR 0.45, 95% CI 0.24 to 0.83; I² = 60%), but no significant reduction in neonatal high care admission. There was no overall effect on the risk of stillbirth or infant death before discharge from hospital (11 trials 15,665 babies: RR 0.90, 95% CI 0.74 to 1.09; I² = 0%).One study showed a reduction in childhood systolic BP greater than 95th percentile among children exposed to calcium supplementation in utero (514 children: RR 0.59, 95% CI 0.39 to 0.91). In a subset of these children, dental caries at 12 years old was also reduced (195 children, RR 0.73, 95% CI 0.62 to 0.87). Low-dose calcium supplementation (< 1 g/day)We included 10 trials (2234 women) that evaluated low-dose supplementation with calcium alone (4) or in association with vitamin D (3), linoleic acid (2), or antioxidants (1). Most studies recruited women at high risk for pre-eclampsia, and were at high risk of bias, thus the results should be interpreted with caution. Supplementation with low doses of calcium significantly reduced the risk of pre-eclampsia (RR 0.38, 95% CI 0.28 to 0.52; I² = 0%). There was also a reduction in hypertension, low birthweight and neonatal intensive care unit admission. AUTHORS' CONCLUSIONS: Calcium supplementation (≥ 1 g/day) is associated with a significant reduction in the risk of pre-eclampsia, particularly for women with low calcium diets. The treatment effect may be overestimated due to small-study effects or publication bias. It also reduces preterm birth and the occurrence of the composite outcome 'maternal death or serious morbidity'. We considered these benefits to outweigh the increased risk of HELLP syndrome, which was small in absolute numbers. The World Health Organization recommends calcium 1.5 g to 2 g daily for pregnant women with low dietary calcium intake.The limited evidence on low-dose calcium supplementation suggests a reduction in pre-eclampsia, but needs to be confirmed by larger, high-quality trials. Pending such results, in settings of low dietary calcium where high-dose supplementation is not feasible, the option of lower-dose supplements (500 to 600 mg/day) might be considered in preference to no supplementation.

Vitamin D and gestational diabetes: an update.

PURPOSE OF REVIEW: Vitamin D status (which is involved in glucose homeostasis) is related to gestational diabetes mellitus (GDM). GDM is characterized by increased resistance to and impaired secretion of insulin and results in higher risk of adverse pregnancy outcomes including operative delivery, macrosomia, shoulder dystocia and neonatal hypoglycemia. Women with GDM and their babies are at increased risk for developing type II diabetes. RECENT FINDINGS: International definitions of vitamin D deficiency and normality are inconsistent. Vitamin D deficiency is common in pregnant women particularly those with poor diets and who have dark skins living in temperate climes with lack of exposure to sunlight. SUMMARY: Few interventional studies indicate that supplementation optimizes maternal vitamin D status or improves maternal glucose metabolism. Observational studies about maternal vitamin D status and risk of GDM are conflicting. This could be because of measurement of vitamin D or differences in population characteristics such as ethnicity, geographic location, gestational age at sampling and diagnostic criteria for GDM. Good-quality randomized controlled trials are required to determine whether vitamin D supplementation decreases the risk of GDM or improves glucose tolerance in diabetic women.

Angiogenic factors and uterine Doppler velocimetry in early- and late-onset preeclampsia.

OBJECTIVE: To assess correlations between maternal serum levels of pro- and anti-angiogenic factors with uterine perfusion in women with early- compared with late-onset preeclampsia, and in healthy pregnant women. DESIGN: Case-control study. SETTING: Antenatal care clinic located within a hospital (São Bernardo do Campo, Brazil). POPULATION: We enrolled 54 preeclamptic and 54 healthy control women who were coming for routine ultrasound at 28-36 weeks' gestation. METHODS: All participants had uterine artery and umbilical Doppler studies and a blood sample to assess maternal serum levels of soluble fms-like tyrosine kinase-1, soluble endoglin, adiponectin and plasminogen activator inhibitor-1. All angiogenic factors were measured using enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Levels of pro- and anti-angiogenic factors in maternal serum, and uterine artery Doppler findings. RESULTS: Concentrations of soluble fms-like tyrosine kinase-1 and soluble endoglin were significantly higher in preeclamptic than control women (p < 0.0001 and p < 0.0001, respectively), especially in those with early-onset (<34 weeks) preeclampsia. These two anti-angiogenic mediators were significantly correlated with increased uterine artery Doppler in the preeclamptic women. Plasminogen activator inhibitor-1 levels were significantly higher in preeclampsia (p = 0.03) but unrelated to uterine artery resistance. Adiponectin levels were similar in cases and controls, independent of body mass index and unrelated to uterine artery resistance. CONCLUSION: Preeclamptic patients have increased soluble fms-like tyrosine kinase-1 and soluble endoglin serum levels and this increase is directly correlated with uterine artery resistance, especially in those with early-onset preeclampsia.

Getting too sweet: galectin-1 dysregulation in gestational diabetes mellitus.

Galectin-1 (gal-1) is a prototype carbohydrate-binding protein, whose dysregulation is associated with adverse pregnancy outcomes such as spontaneous abortion and pre-eclampsia. Furthermore, it is known that faulty gal-1 protein production or gene regulation can be caused by single-nucleotide polymorphisms in the LGALS1 gene. Gestational diabetes mellitus (GDM) is also an adverse pregnancy outcome and the most common metabolic disorder during gestation. However, gal-1 expression patterns during GDM remain largely unknown. Our aims were to define local and peripheral gal-1 expression patterns during pregnancy, and to investigate LGALS1 gene polymorphisms in GDM patients. Circulating gal-1 levels were determined by ELISA in GDM patients and normal pregnant controls, and LGALS1 gene polymorphisms were assessed for association with GDM. Placental tissues were collected from control and GDM term pregnancies to evaluate local gal-1 expression by immunofluorescence. Our results show that GDM is associated with a failure to increase circulating gal-1 levels during the second and third trimester, as well as overexpression of gal-1 in placental tissue. Additionally, the LGALS1 polymorphism rs4820294 was associated with the development of GDM. In pregnancies complicated by GDM, we observed gal-1 dysregulation both locally in the placenta and peripherally in the circulation. Furthermore, the association between the LGALS1 polymorphism and GDM may indicate a genetic contribution to this adverse pregnancy outcome.