The effect of calcium supplementation on blood pressure in non-pregnant women with previous pre-eclampsia: A randomized placebo-controlled study.

BACKGROUND: Low dietary calcium is associated with the hypertensive disorders of pregnancy, and evidence suggests that the risks associated with pre-eclampsia are reduced by calcium supplementation. In the general (non-pregnant) population, low dietary calcium intake is associated with hypertension with inconsistent evidence that calcium supplementation may reduce blood pressure. Women with pre-eclampsia are also at risk of hypertension later in life. An exploratory sub-study among early participants enrolled in the WHO long-term calcium supplementation in women at high risk of pre-eclampsia (CAP) study reported a trend to more blood pressure reduction with calcium in non-pregnant women with previous severe as opposed to non-severe pre-eclampsia. The current study reports the effects of low-dose calcium supplementation in non-pregnant women in the complete trial cohort. METHODS: The CAP Study was a multi-country randomized, double-blind placebo-controlled clinical trial to test the hypothesis that calcium deficiency may play a role in the genesis of pre-eclampsia in early pregnancy. From 2011 to 2016, non-pregnant women who had pre-eclampsia or eclampsia in their most recent pregnancy were randomized to receive either 500 mg/day elemental calcium or placebo. In this sub-study we compared the change in blood pressure from baseline to the 12-week visit between participants receiving calcium versus placebo for those not pregnant at the 12-week visit. RESULTS: Of 1355 women randomized, 810 attended a 12-week visit without being pregnant, of whom 791 had blood pressure measurements available for both baseline and 12-week visits. There was a greater reduction in blood pressure in the calcium group compared with the placebo group for systolic pressure (difference 3.1 mmHg, 95% CI 0.8 to 5.4) and mean arterial pressure (MAP) (difference 2.0 mmHg, 95% CI 0.1 to 3.8). The difference in diastolic blood pressure reduction (1.4 mmHg, 95% CI -0.5 to 3.3) was not statistically significant (p = 0.140). For women with previous pre-eclampsia with severe features (n = 447), there was significantly greater reduction in blood pressure in the calcium than the placebo group (difference for systolic 4.0, 95% CI 0.7 to 7.3; diastolic 3.0, 95% CI 0.5 to 5.5 and mean arterial pressure 3.3, 95% CI 0.8 to 5.9 mmHg). For women with previous pre-eclampsia without severe features (n = 344), there were no significant differences between calcium and placebo groups. ANOVA analysis found no statistically significant interaction between previous pre-eclampsia severity and treatment, for systolic (p = 0.372), diastolic (p = 0.063) or mean blood pressure (p = 0.103). CONCLUSIONS: Low-dose calcium supplementation significantly reduced systolic and mean arterial pressure in non-pregnant women with previous pre-eclampsia. We did not confirm a greater calcium effect in women with previous pre-eclampsia with severe versus non-severe features. The effect of low-dose calcium is of importance since even modest blood pressure reductions at a population level may have important benefits in terms of reduced major complications of hypertension. This study adds to the mounting evidence of health benefits which could be achieved for populations with low dietary calcium through strategies to increase calcium intake, particularly among women at high risk due to previous pre-eclampsia. CLINICAL TRIAL REGISTRATION: The trial was registered with the Pan-African Clinical Trials Registry, registration number PACTR201105000267371 (https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=267).

Does gentle assisted pushing or giving birth in the upright position reduce the duration of the second stage of labour? A three-arm, open-label, randomised controlled trial in South Africa.

INTRODUCTION: Gentle assisted pushing (GAP) is an innovative method of applying gentle, steady pressure to a woman's uterine fundus during second stage of labour. This randomised trial evaluated GAP in an upright position, compared with upright position alone or routine practice (recumbent posture). METHODS: An open-label, hospital-based, randomised trial was conducted in Eastern Cape, South Africa. Randomisation occurred following at least 15 min in second stage of labour. Participants were randomly assigned (1:1:1) using computer-generated block randomisation of variable size using opaque, sealed, numbered envelopes. Primary analysis was intention to treat. Participants were healthy, nulliparous, consenting women with a singleton pregnancy in cephalic presentation where vaginal birth was anticipated. The primary outcome was mean time from randomisation to birth. RESULTS: 1158 participants were randomly allocated to GAP (n=388), upright position (n=386) and routine practice (n=384), with no loss to follow-up. Baseline characteristics were largely similar. In the experimental arm, GAP was applied a median of two times (IQR 1.0-3.0). Women in upright position alone spent a median of 6 min (IQR 3.0-10.0) upright. Mean duration from randomisation to birth was not different across groups (mean (SD) duration: 24.1 (34.9) min in GAP group, 24.6 (30.5) min in upright group, 25.0 (39.3) min in routine practice group). There were no differences in secondary outcomes, except that at two sites maternal discomfort was greater for both GAP and upright position compared with routine practice; at the other sites there were no differences. CONCLUSION: No benefit was identified from GAP in the second stage; some women found the position uncomfortable. The use of fundal pressure should be limited to further research to determine techniques or settings in which it can safely assist vaginal birth. Women should be encouraged to assume the position they find most comfortable. TRIAL REGISTRATION NUMBER: PACTR201502001034448.

Changes in body mass index and hemoglobin concentration in breastfeeding women living with HIV with a CD4 count over 350: Results from 4 African countries (The ANRS 12174 trial).

INTRODUCTION: Breastfeeding is recommended for infants born to HIV-infected women in low-income settings. Both breastfeeding and HIV-infection are energy demanding. Our objective was to explore how exclusive and predominant breastfeeding changes body mass index (BMI) among breastfeeding HIV1-positive women participating in the ANRS12174 trial (clinical trial no NCT0064026). METHODS: HIV-positive women (n = 1 267) with CD4 count >350, intending to breastfeed HIV-negative infants were enrolled from Burkina Faso, South Africa, Uganda and Zambia and counselled on breastfeeding. N = 1 216 were included in the analysis. The trial compared Lamivudine and Lopinavir/Ritonavir as a peri-exposure prophylaxis. We ran a linear mixed-effect model with BMI as the dependent variable and exclusive or predominant breastfeeding duration as the key explanatory variable. RESULTS: Any breastfeeding or exclusive/predominant) breastfeeding was initiated by 99.6% and 98.6% of the mothers respectively in the first week after birth. The median (interquartile range: IQR) duration of the group that did any breastfeeding or the group that did exclusive /predominant breastfeeding were 9.5 (7.5; 10.6) and 5.8 (5.6; 5.9)) months, respectively. The median (IQR) age, BMI, CD4 count, and HIV viral load at baseline (day 7) were 27 (23.3; 31) years, 23.7 (21.3; 27.0) kg/m2, 530 (432.5; 668.5) cells/µl and 0.1 (0.8; 13.7)1000 copies/mL, respectively. No major change in mean BMI was seen in this cohort over a 50-week period during lactation. The mean change between 26 and 50 weeks after birth was 0.7 kg/m2. Baseline mean BMI (measured on day 7 postpartum) and CD4 count were positively associated with maternal BMI change, with a mean increase of 1.0 kg/m2 (0.9; 1.0) per each additional baseline-BMI kilogram and 0.3 kg/m2 (0.2; 0.5) for each additional CD4 cell/µl, respectively. CONCLUSION: Breastfeeding was not negatively correlated with the BMI of HIV-1 infected Sub-Saharan African mothers. However, a higher baseline BMI and a CD4 count >500 cells/µl were associated with maternal BMI during the exclusive/ predominant breastfeeding period. Considering the benefits of breast milk for the infants and the recurrent results from different studies that breastfeeding is not harmful to the HIV-1-infected mothers, this study also supports the WHO 2016 guidelines on infant feeding that mothers living with HIV should breastfeed where formula is not safe for at least 12 months and up to 24 months, given that the right treatment or prophylaxis for the infection is administered. These findings and conclusions cannot be extrapolated to women who are immune-compromised or have AIDS.

Fundal pressure during the second stage of labour.

BACKGROUND: Fundal pressure during the second stage of labour (also known as the 'Kristeller manoeuvre') involves application of manual pressure to the uppermost part of the uterus directed towards the birth canal, in an attempt to assist spontaneous vaginal birth and avoid prolonged second stage or the need for operative birth. Fundal pressure has also been applied using an inflatable belt. Fundal pressure is widely used, however methods of its use vary widely. Despite strongly held opinions in favour of and against the use of fundal pressure, there is limited evidence regarding its maternal and neonatal benefits and harms. There is a need for objective evaluation of the effectiveness and safety of fundal pressure in the second stage of labour. OBJECTIVES: To determine if fundal pressure is effective in achieving spontaneous vaginal birth, and preventing prolonged second stage or the need for operative birth, and to explore maternal and neonatal adverse effects related to fundal pressure. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register (30 November 2016) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of fundal pressure (manual or by inflatable belt) versus no fundal pressure in women in the second stage of labour with singleton cephalic presentation. DATA COLLECTION AND ANALYSIS: Two or more review authors independently assessed potential studies for inclusion and quality. We extracted data using a pre-designed form. We entered data into Review Manager 5 software and checked for accuracy. MAIN RESULTS: Nine trials are included in this updated review. Five trials (3057 women) compared manual fundal pressure versus no fundal pressure. Four trials (891 women) compared fundal pressure by means of an inflatable belt versus no fundal pressure. It was not possible to blind women and staff to this intervention. We assessed two trials as being at high risk of attrition bias and another at high risk of reporting bias. All other trials were low or unclear for other risk of bias domains. Most of the trials had design limitations. Heterogeneity was high for the majority of outcomes. Manual fundal pressure versus no fundal pressureManual fundal pressure was not associated with changes in: spontaneous vaginal birth within a specified time (risk ratio (RR) 0.96, 95% confidence interval (CI) 0.71 to 1.28; 120 women; 1 trial; very low-quality evidence), instrumental births (RR 3.28, 95% CI 0.14 to 79.65; 197 women; 1 trial), caesarean births (RR 1.10, 95% CI 0.07 to 17.27; 197 women; 1 trial), operative birth (average RR 0.66, 95% CI 0.12 to 3.55; 317 women; 2 studies; I² = 43%; Tau² = 0.71; very low-quality evidence), duration of second stage (mean difference (MD) -0.80 minutes, 95% CI -3.66 to 2.06 minutes; 194 women; 1 study; very low-quality evidence), low arterial cord pH in newborn babies (RR 1.07, 95% CI 0.72 to 1.58; 297 women; 2 trials; very low-quality evidence), or Apgar scores less than seven at five minutes (average RR 4.48, 95% CI 0.28 to 71.45; 2759 infants; 4 trials; I² = 89%; Tau² = 3.55; very low-quality evidence). More women who received manual fundal pressure had cervical tears than in the control group (RR 4.90, 95% CI 1.09 to 21.98; 295 women; 1 trial). No neonatal deaths occurred in either of the two studies reporting this outcome (very low-quality evidence). No trial reported the outcome severe maternal morbidity or death. Fundal pressure by inflatable belt versus no fundal pressureFundal pressure by inflatable belt did not reduce the number of women havinginstrumental births (average RR 0.73, 95% CI 0.52 to 1.02; 891 women; 4 trials; I² = 52%; Tau² = 0.05) or operative births (average RR 0.62, 95% CI 0.38 to 1.01; 891 women; 4 trials; I² = 78%; Tau² = 0.14; very low-quality evidence). Heterogeneity was high for both outcomes. Duration of second stage was reported in two trials, which both showed that inflatable belts shortened duration of labour in nulliparous women (average MD -50.80 minutes, 95% CI -94.85 to -6.74 minutes; 253 women; 2 trials; I² = 97%; Tau² = 975.94; very low-quality evidence). No data on this outcome were available for multiparous women. The inflatable belt did not make any difference to rates of caesarean births (average RR 0.56, 95% CI 0.14 to 2.26; 891 women; 4 trials; I² = 70%; Tau² = 0.98), low arterial cord pH in newborn babies (RR 0.47, 95% CI 0.09 to 2.55; 461 infants; 1 trial; low-quality evidence), or Apgar scores less than seven at five minutes (RR 4.62, 95% CI 0.22 to 95.68; 500 infants; 1 trial; very low-quality evidence). Third degree perineal tears were increased in the inflatable belt group (RR 15.69, 95% CI 2.10 to 117.02; 500 women; 1 trial). Spontaneous vaginal birth within a specified time, neonatal death, andsevere maternal morbidity or death were not reported in any trial. AUTHORS' CONCLUSIONS: There is insufficient evidence to draw conclusions on the beneficial or harmful effects of fundal pressure, either manually or by inflatable belt. Fundal pressure by an inflatable belt during the second stage of labour may shorten duration of second stage for nulliparous women, and lower rates of operative birth. However, existing studies are small and their generalizability is uncertain. There is insufficient evidence regarding safety for the baby. There is no evidence on the use of fundal pressure in specific clinical settings such as inability of the mother to bear down due to exhaustion or unconsciousness. There is currently insufficient evidence for the routine use of fundal pressure by any method on women in the second stage of labour. Because of current widespread use of the procedure and the potential for use in settings where other methods of assisted birth are not available, further good quality trials are needed. Further evaluation in other groups of women (such as multiparous women) will also be required. Future research should describe in detail how fundal pressure was applied and consider safety of the unborn baby, perineal outcomes, longer-term maternal and infant outcomes and maternal satisfaction.

Extended pre-exposure prophylaxis with lopinavir-ritonavir versus lamivudine to prevent HIV-1 transmission through breastfeeding up to 50 weeks in infants in Africa (ANRS 12174): a randomised controlled trial.

BACKGROUND: Strategies to prevent postnatal mother-to-child transmission of HIV-1 in Africa, including infant prophylaxis, have never been assessed past 6 months of breastfeeding, despite breastfeeding being recommended up to 12 months after birth. We aimed to compare the efficacy and safety of infant prophylaxis with the two drug regimens (lamivudine or lopinavir-ritonavir) to prevent postnatal HIV-1 transmission up to 50 weeks of breastfeeding. METHODS: We did a randomised controlled trial in four sites in Burkina Faso, South Africa, Uganda, and Zambia in children born to HIV-1-infected mothers not eligible for antiretroviral therapy (CD4 count >350 cells per µL). An independent researcher electronically generated a randomisation schedule; we then used sequentially numbered envelopes to randomly assign (1:1) HIV-1-uninfected breastfed infants aged 7 days to either lopinavir-ritonavir or lamivudine (paediatric liquid formulations, twice a day) up to 1 week after complete cessation of breastfeeding or at the final visit at week 50. We stratified the randomisation by country and used permuted blocks of four and six. We used a study label on drug bottles to mask participants, study physicians, and assessors to the treatment allocation. The primary outcome was infant HIV-1 infection between age 7 days and 50 weeks, diagnosed every 3 months with HIV-1 DNA PCR, in the modified intention-to-treat population (all who attended at least one follow-up visit). This trial is registered with ClinicalTrials.gov, number NCT00640263. FINDINGS: Between Nov 16, 2009, and May 7, 2012, we enrolled and randomised 1273 infants and analysed 1236; 615 assigned to lopinavir-ritonavir or 621 assigned to lamivudine. 17 HIV-1 infections were diagnosed in the study period (eight in the lopinavir-ritonavir group and nine in the lamivudine group), resulting in cumulative HIV-1 infection of 1.4% (95% CI 0.4-2.5) and 1.5% (0.7-2.5), respectively. Infection rates did not differ between the two drug regimens (hazard ratio [HR] of lopinavir-ritonavir versus lamivudine of 0.90, 95% CI 0.35-2.34; p=0.83). Clinical and biological severe adverse events did not differ between groups; 251 (51%) infants had a grade 3-4 event in the lopinavir-ritonavir group compared with 246 (50%) in the lamivudine group. INTERPRETATION: Infant HIV-1 prophylaxis with lopinavir-ritonavir was not superior to lamivudine and both drugs led to very low rates of HIV-1 postnatal transmission for up to 50 weeks of breastfeeding. Infant pre-exposure prophylaxis should be extended until the end of HIV-1 exposure and mothers should be informed about the persistent risk of transmission throughout breastfeeding. FUNDING: INSERM/National Agency for Research on AIDS and Viral Hepatitis (including funds from the Total Foundation), European Developing Countries Clinical Trials Partnership, Research Council of Norway.

Breastfeeding patterns and its determinants among mothers living with Human Immuno-deficiency Virus -1 in four African countries participating in the ANRS 12174 trial.

BACKGROUND: HIV-1 transmission rates have been reduced over the last decade, an estimated 2 million new infections per year arise, including 220,000 paediatric cases. The main post-natal HIV exposure is through breastfeeding, where both its duration and modality (exclusive or not) are associated with postnatal transmission. The ANRS 12174 trial compared HIV-1 postnatal transmission of 2 prophylaxis drugs for infants during lactation (lamivudine and lopinavir-ritonavir). Our objective has been to examine the feeding practices and the determinants of exclusive/ predominant (EPBF) or any breastfeeding among the participants of this trial in Burkina Faso, South Africa, Uganda and Zambia. METHODS: Mothers infected with HIV-1 and their uninfected offspring were followed from day 7 after birth for 50 weeks, keeping monthly records of their feeding patterns. Feeding was classified into 3 categories: 1) exclusive breastfeeding during the first six months, only breast-milk being given to infant for 6 months, 2) predominant breastfeeding, breast-milk with liquid-based items being given, and 3) mixed feeding, other non-breast milk or solid food being given in addition to breast milk with or without liquid-based items. The categories were merged into 2 groups: EPBF applying to infants aged <6 months and mixed feeding applying to infants of any age. The feeding patterns have been given as Kaplan-Meier curves. A flexible parametric multiple regression model was used to identify the determinants of the mothers' feeding behaviour. RESULTS: A total of 1,225 mother-infant pairs provided feeding data from Burkina Faso (N = 204), South Africa (N = 213), Uganda (N = 274) and Zambia (N = 534) between November 2009 and March 2013. The mean maternal age was 27.4 years and the mean BMI was 24.5. 57.7 and 93.9% of mothers initiated breastfeeding within the first hour and first day, respectively. Overall, the median durations of any form of breastfeeding and EPBF were 40.6, and 20.9 weeks, respectively. Babies randomized to the lopinavir/ritonavir group in South Africa tended to do less EPBF than those in the lamivudine group. Overall the group of mothers aged between 25 and 30 years, those married, employed or multiparous tended to stop early EPBF. Mothers living in Uganda or Zambia, those aged between 25 -30 years, better educated (at least secondary school level), employed or having undergone C-section stopped any breastfeeding early. CONCLUSIONS: There is a need to improve breastfeeding and complementary feeding practices of children, particularly those exposed to HIV and anti-retrovirals, taking into account context and socio-demographic factors. TRIAL REGISTRATION: Clinical trial registration: NCT00640263.

A multicentre randomized controlled trial of gentle assisted pushing in the upright posture (GAP) or upright posture alone compared with routine practice to reduce prolonged second stage of labour (the Gentle Assisted Pushing study): study protocol.

BACKGROUND: Fundal pressure (pushing on the upper part of the uterus in the direction of the birth canal) is often performed in routine practice, however the benefit and indications for its use are unclear and vigorous pressure is potentially harmful. There is some evidence that it may be applied routinely or to expedite delivery in some situations (e.g. fetal distress or maternal exhaustion), particularly in settings where other methods of achieving delivery (forceps, vacuum) are not available. Gentle assisted pushing (GAP) is an innovative method of applying gentle but steady pressure to the uterine fundus with the woman in an upright posture. This trial aims to evaluate the use of GAP in an upright posture, or upright posture alone, on reducing the mean time of delivery and the associated maternal and neonatal complications in women not having delivered following 15-30 min in the second stage of labour. METHODS/DESIGN: We will conduct a multicentre, randomized, unblinded, controlled trial with three parallel arms (1:1:1). 1,145 women will be randomized at three hospitals in South Africa. Women will be eligible for inclusion if they are ≥18 years old, nulliparous, gestational age ≥ 35 weeks, have a singleton pregnancy in cephalic presentation and vaginal delivery anticipated. Women with chronic medical conditions or obstetric complications are not eligible. If eligible women are undelivered following 15-30 min in the second stage of labour, they will be randomly assigned to: 1) GAP in the upright posture, 2) upright posture only and 3) routine practice (recumbent/supine posture). The primary outcome is the mean time from randomization to complete delivery. Secondary outcomes include operative delivery, adverse neonatal outcomes, maternal adverse events and discomfort. DISCUSSION: This trial will establish whether upright posture and/or a controlled method of applying fundal pressure (GAP) can improve labour outcomes for women and their babies. If fundal pressure is found to have a measurable beneficial effect, this gentle approach can be promoted as a replacement for the uncontrolled methods currently in use. If it is not found to be useful, fundal pressure can be discouraged.

Hormonal contraception for women exposed to HIV infection.

BACKGROUND: Concern about a possible association of hormonal contraception with HIV acquisition has been raised by three types of evidence. Firstly, high-dose progestogen treatment greatly increases HIV acquisition in female non-human primates. Secondly, biological plausibility for a link between hormonal contraception anf HIV acquisition is provided by evidence of a hypo-oestrogenic state induced by progestogen contraception with vaginal mucosal thinning, and evidence of effects on the humoral and cellular immune systems. Thirdly, some but not other large observational studies have found an increase in HIV acquisition among women using hormonal contraception. OBJECTIVES: To determine, from the best available evidence, the effect of hormonal contraception on HIV acquisition. SEARCH METHODS: We used the Cochrane Fertility Regulation Group trials search strategy. SELECTION CRITERIA: Published, unpublished and ongoing trials with random allocation, comparing hormonal with non-hormonal methods, other hormonal methods or no contraception in women at risk of HIV acquisition. DATA COLLECTION AND ANALYSIS: Data will be extracted from eligible trials onto a data extraction sheet and analysed using routine Cochrane Collaboration methodology, MAIN RESULTS: One ongoing randomised trial was identified, with no data available to date. AUTHORS' CONCLUSIONS: There is currently no robust evidence from randomized trials on the possible effect of hormonal contraception on HIV acquisition. High quality trials in this area are needed to inform counselling of individual woman and public health policy.

Restricting oral fluid and food intake during labour.

BACKGROUND: Restricting fluids and foods during labour is common practice across many birth settings with some women only being allowed sips of water or ice chips. Restriction of oral intake may be unpleasant for some women, and may adversely influence their experience of labour. OBJECTIVES: To determine the benefits and harms of oral fluid or food restriction during labour. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2013) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs of restricting fluids and food for women in labour compared with women free to eat and drink. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. MAIN RESULTS: We identified 19 studies of which we included five, involving 3130 women. We excluded eight studies, one awaits classification and five are ongoing studies. All the included studies looked at women in active labour and at low risk of potentially requiring a general anaesthetic. One study looked at complete restriction versus giving women the freedom to eat and drink at will; two studies looked at water only versus giving women specific fluids and foods and two studies looked at water only versus giving women carbohydrate drinks.When comparing any restriction of fluids and food versus women given some nutrition in labour, the meta-analysis was dominated by one study undertaken in a highly medicalised environment. There were no statistically significant differences identified in: caesarean section (average risk ratio (RR) 0.89, 95% confidence interval (CI) 0.63 to 1.25, five studies, 3103 women), operative vaginal births (average RR 0.98, 95% CI 0.88 to 1.10, five studies, 3103 women) and Apgar scores less than seven at five minutes (average RR 1.43, 95% CI 0.77 to 2.68, four studies, 2902 infants), nor in any of the other outcomes assessed. Women's views were not assessed. The pooled data were insufficient to assess the incidence of Mendelson's syndrome, an extremely rare outcome. Other comparisons showed similar findings, except one study did report a significant increase in caesarean sections for women taking carbohydrate drinks in labour compared with water only, but these results should be interpreted with caution as the sample size was small. AUTHORS' CONCLUSIONS: Since the evidence shows no benefits or harms, there is no justification for the restriction of fluids and food in labour for women at low risk of complications. No studies looked specifically at women at increased risk of complications, hence there is no evidence to support restrictions in this group of women. Conflicting evidence on carbohydrate solutions means further studies are needed and it is critical in any future studies to assess women's views.

Routine vaginal examinations for assessing progress of labour to improve outcomes for women and babies at term.

BACKGROUND: Vaginal examinations have become a routine intervention in labour as a means of assessing labour progress. Used at regular intervals, either alone or as a component of the partogram (a pre-printed form providing a pictorial overview of the progress of labour), the aim is to assess if labour is progressing physiologically, and to provide an early warning of slow progress. Abnormally slow progress can be a sign of labour dystocia, which is associated with maternal and fetal morbidity and mortality, particularly in low-income countries where appropriate interventions cannot easily be accessed. However, over-diagnosis of dystocia can lead to iatrogenic morbidity from unnecessary intervention (e.g. operative vaginal birth or caesarean section). It is, therefore, important to establish whether or not the routine use of vaginal examinations is an effective intervention, both as a diagnostic tool for true labour dystocia, and as an accurate measure of physiological labour progress. OBJECTIVES: To compare the effectiveness, acceptability and consequences of digital vaginal examination(s) (alone or within the context of the partogram) with other strategies, or different timings, to assess progress during labour at term. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 February 2013) and reference lists of identified studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of vaginal examinations (including digital assessment of the consistency of the cervix, and the degree of dilation and position of the opening of the uterus (cervical os); and position and station of the fetal presenting part, with or without abdominal palpation) compared with other ways of assessing progress of labour. We also included studies assessing different timings of vaginal examinations. We excluded quasi-RCTs and cross-over trials. We also excluded trials with a primary focus on assessing progress of labour using the partogram (of which vaginal examinations is one component) as this is covered by another Cochrane review. However, studies where vaginal examinations were used within the context of the partogram were included if the studies were randomised according to the vaginal examination component. DATA COLLECTION AND ANALYSIS: Three review authors assessed the studies for inclusion in the review. Two authors undertook independent data extraction and assessed the risk of bias of each included study. A third review author also checked data extraction and risk of bias. Data entry was checked. MAIN RESULTS: We found two studies that met our inclusion criteria but they were of unclear quality. One study, involving 307 women, compared vaginal examinations with rectal examinations, and the other study, involving 150 women, compared two-hourly with four-hourly vaginal examinations. Both studies were of unclear quality in terms of risk of selection bias, and the study comparing the timing of the vaginal examinations excluded 27% (two hourly) to 28% (four hourly) of women after randomisation because they no longer met the inclusion criteria.When comparing routine vaginal examinations with routine rectal examinations to assess the progress of labour, we identified no difference in neonatal infections requiring antibiotics (risk ratio (RR) 0.33, 95% confidence interval (CI) 0.01 to 8.07, one study, 307 infants). There were no data on the other primary outcomes of length of labour, maternal infections requiring antibiotics and women's overall views of labour. The study did show that significantly fewer women reported that vaginal examination was very uncomfortable compared with rectal examinations (RR 0.42, 95% CI 0.25 to 0.70, one study, 303 women). We identified no difference in the secondary outcomes of augmentation, caesarean section, spontaneous vaginal birth, operative vaginal birth, perinatal mortality and admission to neonatal intensive care.Comparing two-hourly vaginal examinations with four-hourly vaginal examinations in labour, we found no difference in length of labour (mean difference in minutes (MD) -6.00, 95% CI -88.70 to 76.70, one study, 109 women). There were no data on the other primary outcomes of maternal or neonatal infections requiring antibiotics, and women's overall views of labour. We identified no difference in the secondary outcomes of augmentation, epidural for pain relief, caesarean section, spontaneous vaginal birth and operative vaginal birth. AUTHORS' CONCLUSIONS: On the basis of women's preferences, vaginal examination seems to be preferred to rectal examination. For all other outcomes, we found no evidence to support or reject the use of routine vaginal examinations in labour to improve outcomes for women and babies. The two studies included in the review were both small, and carried out in high-income countries in the 1990s.  It is surprising that there is such a widespread use of this intervention without good evidence of effectiveness, particularly considering the sensitivity of the procedure for the women receiving it, and the potential for adverse consequences in some settings.The effectiveness of the use and timing of routine vaginal examinations in labour, and other ways of assessing progress in labour, including maternal behavioural cues, should be the focus of new research as a matter of urgency. Women's views of ways of assessing labour progress should be given high priority in any future research in this area.

Active management of the third stage of labour with and without controlled cord traction: a randomised, controlled, non-inferiority trial.

BACKGROUND: Active management of the third stage of labour reduces the risk of post-partum haemorrhage. We aimed to assess whether controlled cord traction can be omitted from active management of this stage without increasing the risk of severe haemorrhage. METHODS: We did a multicentre, non-inferiority, randomised controlled trial in 16 hospitals and two primary health-care centres in Argentina, Egypt, India, Kenya, the Philippines, South Africa, Thailand, and Uganda. Women expecting to deliver singleton babies vaginally (ie, not planned caesarean section) were randomly assigned (in a 1:1 ratio) with a centrally generated allocation sequence, stratified by country, to placental delivery with gravity and maternal effort (simplified package) or controlled cord traction applied immediately after uterine contraction and cord clamping (full package). After randomisation, allocation could not be concealed from investigators, participants, or assessors. Oxytocin 10 IU was administered immediately after birth with cord clamping after 1-3 min. Uterine massage was done after placental delivery according to local policy. The primary (non-inferiority) outcome was blood loss of 1000 mL or more (severe haemorrhage). The non-inferiority margin for the risk ratio was 1·3. Analysis was by modified intention-to-treat, excluding women who had emergency caesarean sections. This trial is registered with the Australian and New Zealand Clinical Trials Registry, ACTRN 12608000434392. FINDINGS: Between June 1, 2009, and Oct 30, 2010, 12,227 women were randomly assigned to the simplified package group and 12,163 to the full package group. After exclusion of women who had emergency caesarean sections, 11,861 were in the simplified package group and 11,820 were in the full package group. The primary outcome of blood loss of 1000 mL or more had a risk ratio of 1·09 (95% CI 0·91-1·31) and the upper 95% CI limit crossed the pre-stated non-inferiority margin. One case of uterine inversion occurred in the full package group. Other adverse events were haemorrhage-related. INTERPRETATION: Although the hypothesis of non-inferiority was not met, omission of controlled cord traction has very little effect on the risk of severe haemorrhage. Scaling up of haemorrhage prevention programmes for non-hospital settings can safely focus on use of oxytocin. FUNDING: United States Agency for International Development and UN Development Programme/UN Population Fund/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research.

Administration of 400 µg of misoprostol to augment routine active management of the third stage of labor.

OBJECTIVE: To assess the effectiveness and safety of the administration of misoprostol, an orally active prostaglandin, in addition to routine uterotonic therapy as part of the active management of the third stage of labor. METHODS: The present study was a hospital-based, decentralized, multi-center, randomized, placebo-controlled, double-blind trial. We enrolled 1103 women (out of a target sample size of 1180) at 4 hospitals in South Africa, Uganda, and Nigeria. Participants received a sublingual dose of 400 µg of misoprostol or a placebo, in addition to standard active management of the third stage of labor, after vaginal birth. RESULTS: The baseline characteristics of the participants were comparable. The difference in the primary outcome of blood loss of 500 mL or more within 1 hour of randomization was not significant between the 2 groups (misoprostol 22/546 [4.0%] versus placebo 35/553 [6.3%]; relative risk, 0.64; 95% confidence interval, 0.38-1.07). Shivering and pyrexia occurred more frequently in the misoprostol group. No maternal deaths occurred. CONCLUSION: The present study did not confirm a beneficial effect of administering 400 µg of misoprostol, in addition to routine uterotonic therapy, during the third stage of labor, but was consistent with other trials showing a cumulative modest benefit. Where routine uterotonics are available for prophylactic use, any potential benefit of misoprostol might not outweigh the likelihood of adverse effects.

A double-blind, randomized, placebo-controlled trial of misoprostol and routine uterotonics for the prevention of postpartum hemorrhage.

OBJECTIVE: To assess the effects of 400-µg sublingual misoprostol plus routine uterotonics on postpartum hemorrhage. METHODS: A double-blind, placebo-controlled, randomized study was performed. After delivery of the child, eligible women received routine uterotonics and were randomly allocated to receive 400-µg misoprostol or placebo sublingually. The primary outcome measure was blood loss of at least 500 mL within 1 hour of taking the trial tablets. RESULTS: In total, 672 women received misoprostol and 673 received placebo. The baseline data were similar for both groups. Misoprostol plus routine uterotonics reduced postpartum blood loss, but the effect was not significant for blood loss of at least 500 mL (relative risk [RR] 0.96; 95% confidence interval [CI], 0.63-1.45) or blood loss of at least 1000 mL (RR 0.50; 95% CI, 0.15-1.66). Misoprostol also reduced the need for non-routine oxytocin, manual removal of the placenta, and hysterectomy, but these differences were not significant either. Misoprostol was associated with pyrexia and moderate/severe shivering. There was no death in either group. CONCLUSION: Misoprostol plus routine uterotonics resulted in modest reductions of blood loss in the third stage of labor, but the effects did not reach statistical significance. Larger studies are recommended.

Uterine massage to reduce postpartum hemorrhage after vaginal delivery.

OBJECTIVE: To determine the effectiveness of sustained uterine massage started before delivery of the placenta in reducing postpartum hemorrhage. METHODS: A randomized controlled trial conducted in Egypt and South Africa between September 2006 and February 2009. A total of 1964 pregnant women were randomly allocated to 1 of 3 treatment groups: intramuscular oxytocin, sustained uterine massage, or both treatments. Blood loss within 30 minutes of delivery was recorded. RESULTS: The incidence of blood loss of 300 mL or more within 30 minutes of delivery was significantly higher in the massage group than in the massage plus oxytocin (RR 1.88; 95% CI, 1.29-2.74 in Assiut, and RR 1.3; 95% CI, 1.00-1.68 in SA) and the oxytocin only group (RR 1.7; 95% CI, 1.11-2.61 in Assiut, and RR 2.24; 95% CI, 1.54-3.27 in SA). In both centers, use of additional uterotonics was significantly higher in the uterine massage group compared with the other 2 groups. CONCLUSION: Uterine massage was less effective than oxytocin for reducing blood loss after delivery. When oxytocin was used, there was no additional benefit from uterine massage. The effectiveness of uterine massage in the absence of oxytocin was not studied. ACTRN: 12609000372280.

Copper containing intra-uterine devices versus depot progestogens for contraception.

BACKGROUND: Highly effective contraception is essential to reduce unintended pregnancies and the effect these have on individuals, society and public health resources. Intrauterine devices (IUDs) and depot progestogens are two commonly used long-acting, reversible contraceptive methods with different risk and benefit profiles. OBJECTIVES: To compare the contraceptive and non-contraceptive benefits and risks of using the copper-containing IUD versus depot progestogens for contraception. SEARCH STRATEGY: In June 2009 we searched the Cochrane Pregnancy and Childbirth Group Trials Register, the Cochrane Central Register of Controlled Trials, Pubmed, Popline, Clinical Trials.gov, the Current Controlled Trials metaRegister, EMBASE and LILACS, and contacted study authors. SELECTION CRITERIA: Randomized trials comparing women using copper-containing IUDs with women using depot progestogens. DATA COLLECTION AND ANALYSIS: We assessed eligibility and trial quality, extracted and double-entered data. MAIN RESULTS: Two studies were included in the review. In the one study in HIV infected women, the IUD was compared with depot progestogen or the oral contraceptive, according to the women's choice. As the majority of women chose depot progestogen, we have included this study in the review, within a mixed hormonal contraception sub-group.Overall, the copper IUD was more effective than depot progestogens/hormonal contraception at preventing pregnancy (risk ratio (RR) 0.45; 95% confidence interval (CI) 0.24 to 0.84). HIV disease progression was reduced in the IUD group (RR 0.58; 95% CI 0.39 to 0.87). There was no significant difference in pelvic inflammatory disease rates between the two groups. Discontinuation of the allocated method was less frequent with the IUD in one study, and less frequent with hormonal contraception in the other study (in which women were allowed to switch between various hormonal methods). AUTHORS' CONCLUSIONS: In the populations studied, the IUD was more effective than hormonal contraception with respect to pregnancy prevention. High quality research is urgently needed to compare the effects, if any, of these two commonly used contraception methods on HIV acquisition/seroconversion and HIV/AIDS disease progression.

Misoprostol as an adjunct to standard uterotonics for treatment of post-partum haemorrhage: a multicentre, double-blind randomised trial.

BACKGROUND: Post-partum haemorrhage is a leading cause of global maternal morbidity and mortality. Misoprostol, a prostaglandin analogue with uterotonic activity, is an attractive option for treatment because it is stable, active orally, and inexpensive. We aimed to assess the effectiveness of misoprostol as an adjunct to standard uterotonics compared with standard uterotonics alone for treatment of post-partum haemorrhage. METHODS: Women delivering vaginally who had clinically diagnosed post-partum haemorrhage due to uterine atony were enrolled from participating hospitals in Argentina, Egypt, South Africa, Thailand, and Vietnam between July, 2005, and August, 2008. Computer-generated randomisation was used to assign women to receive 600 microg misoprostol or matching placebo sublingually; both groups were also given routine injectable uterotonics. Allocation was concealed by distribution of sealed and sequentially numbered treatment packs in the order that women were enrolled. Providers and women were masked to treatment assignment. The primary outcome was blood loss of 500 mL or more within 60 min after randomisation. Analysis was by intention to treat. This study is registered, number ISRCTN34455240. FINDINGS: 1422 women were assigned to receive misoprostol (n=705) or placebo (n=717). The proportion of women with blood loss of 500 mL or more within 60 min was similar between the misoprostol group (100 [14%]) and the placebo group (100 [14%]; relative risk 1.02, 95% CI 0.79-1.32). In the first 60 min, an increased proportion of women on misoprostol versus placebo, had shivering (455/704 [65%] vs 230/717 [32%]; 2.01, 1.79-2.27) and body temperature of 38 degrees C or higher (303/704 [43%] vs 107/717 [15%]; 2.88, 2.37-2.50). INTERPRETATION: Findings from this study do not support clinical use of 600 microg sublingual misoprostol in addition to standard injectable uterotonics for treatment of post-partum haemorrhage. FUNDING: Bill & Melinda Gates Foundation, and UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction.

Restricting oral fluid and food intake during labour.

BACKGROUND: Restricting fluids and foods during labour is common practice across many birth settings with some women only being allowed sips of water or ice chips. Restriction of oral intake may be unpleasant for some women, and may adversely influence their experience of labour. OBJECTIVES: To determine the benefits and harms of oral fluid or food restriction during labour. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (April 2009). SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs of restricting fluids and food for women in labour compared with women free to eat and drink. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. MAIN RESULTS: We identified five studies (3130 women). All studies looked at women in active labour and at low risk of potentially requiring a general anaesthetic. One study looked at complete restriction versus giving women the freedom to eat and drink at will; two studies looked at water only versus giving women specific fluids and foods and two studies looked at water only versus giving women carbohydrate drinks.When comparing any restriction of fluids and food versus women given some nutrition in labour, the meta-analysis was dominated by one study undertaken in a highly medicalised environment. There were no statistically significant differences identified in: caesarean section (average risk ratio (RR) 0.89, 95% confidence interval (CI) 0.63 to 1.25, five studies, 3103 women), operative vaginal births (average RR 0.98, 95% CI 0.88 to 1.10, five studies, 3103 women) and Apgar scores less than seven at five minutes (average RR 1.43, 95% CI 0.77 to 2.68, three studies, 2574 infants), nor in any of the other outcomes assessed. Women's views were not assessed. The pooled data were insufficient to assess the incidence of Mendelson's syndrome, an extremely rare outcome. Other comparisons showed similar findings, except one study did report a significant increase in caesarean sections for women taking carbohydrate drinks in labour compared with water only, but these results should be interpreted with caution as the sample size was small. AUTHORS' CONCLUSIONS: Since the evidence shows no benefits or harms, there is no justification for the restriction of fluids and food in labour for women at low risk of complications. No studies looked specifically at women at increased risk of complications, hence there is no evidence to support restrictions in this group of women. Conflicting evidence on carbohydrate solutions means further studies are needed and it is critical in any future studies to assess women's views.

Misoprostol for treating postpartum haemorrhage: a randomized controlled trial [ISRCTN72263357].

BACKGROUND: Postpartum haemorrhage remains an important cause of maternal death despite treatment with conventional therapy. Uncontrolled studies and one randomised comparison with conventional oxytocics have reported dramatic effects with high-dose misoprostol, usually given rectally, for treatment of postpartum haemorrhage, but this has not been evaluated in a placebo-controlled trial. METHODS: The study was conducted at East London Hospital Complex, Tembisa and Chris Hani Baragwanath Hospitals, South Africa. Routine active management of the third stage of labour was practised. Women with more than usual postpartum bleeding thought to be related to inadequate uterine contraction were invited to participate, and to sign informed consent. All routine treatment was given from a special 'Postpartum Haemorrhage Trolley'. In addition, participants who consented were enrolled by drawing the next in a series of randomised treatment packs containing either misoprostol 5 x 200 microg or similar placebo, which were given 1 orally, 2 sublingually and 2 rectally. RESULTS: With misoprostol there was a trend to reduced blood loss >/=500 ml in 1 hour after enrolment measured in a flat plastic 'fracture bedpan', the primary outcome (6/117 vs 11/120, relative risk 0.56; 95% confidence interval 0.21 to 1.46). There was no difference in mean blood loss or haemoglobin level on day 1 after birth < 6 g/dl or blood transfusion. Side-effects were increased, namely shivering (63/116 vs 30/118; 2.14, 1.50 to 3.04) and pyrexia > 38.5 degrees C (11/114 vs 2/118; 5.69, 1.29 to 25). In the misoprostol group 3 women underwent hysterectomy of whom 1 died, and there were 2 further maternal deaths. CONCLUSIONS: Because of a lower than expected incidence of the primary outcome in the placebo group, the study was underpowered. We could not confirm the dramatic effect of misoprostol reported in several unblinded studies, but the results do not exclude a clinically important effect. Larger studies are needed to assess substantive outcomes and risks before misoprostol enters routine use.