Community views on active case finding for tuberculosis in low- and middle-income countries: a qualitative evidence synthesis.

BACKGROUND: Active case finding (ACF) refers to the systematic identification of people with tuberculosis in communities and amongst populations who do not present to health facilities, through approaches such as door-to-door screening or contact tracing. ACF may improve access to tuberculosis diagnosis and treatment for the poor and for people remote from diagnostic and treatment facilities. As a result, ACF may also reduce onward transmission. However, there is a need to understand how these programmes are experienced by communities in order to design appropriate services. OBJECTIVES: To synthesize community views on tuberculosis active case finding (ACF) programmes in low- and middle-income countries. SEARCH METHODS: We searched MEDLINE, Embase, and eight other databases up to 22 June 2023, together with reference checking, citation searching, and contact with study authors to identify additional studies. We did not include grey literature. SELECTION CRITERIA: This review synthesized qualitative research and mixed-methods studies with separate qualitative data. Eligible studies explored community experiences, perceptions, or attitudes towards ACF programmes for tuberculosis in any endemic low- or middle-income country, with no time restrictions. DATA COLLECTION AND ANALYSIS: Due to the large volume of studies identified, we chose to sample studies that had 'thick' description and that investigated key subgroups of children and refugees. We followed standard Cochrane methods for study description and appraisal of methodological limitations. We conducted thematic synthesis and developed codes inductively using ATLAS.ti software. We examined codes for underlying ideas, connections, and interpretations and, from this, generated analytical themes. We assessed the confidence in the findings using the GRADE-CERQual approach, and produced a conceptual model to display how the different findings interact. MAIN RESULTS: We included 45 studies in this synthesis, and sampled 20. The studies covered a broad range of World Health Organization (WHO) regions (Africa, South-East Asia, Eastern Mediterranean, and the Americas) and explored the views and experiences of community members, community health workers, and clinical staff in low- and middle-income countries endemic for tuberculosis. The following five themes emerged. • ACF improves access to diagnosis for many, but does little to help communities on the edge. Tuberculosis ACF and contact tracing improve access to health services for people with worse health and fewer resources (High confidence). ACF helps to find this population, exposed to deprived living conditions, but is not sensitive to additional dimensions of their plight (High confidence) and out-of-pocket costs necessary to continue care (High confidence). Finally, migration and difficult geography further reduce communities' access to ACF (High confidence). • People are afraid of diagnosis and its impact. Some community members find screening frightening. It exposes them to discrimination along distinct pathways (isolation from their families and wider community, lost employment and housing). HIV stigma compounds tuberculosis stigma and heightens vulnerability to discrimination along these same pathways (High confidence). Consequently, community members may refuse to participate in screening, contact tracing, and treatment (High confidence). In addition, people with tuberculosis reported their emotional turmoil upon diagnosis, as they anticipated intense treatment regimens and the prospect of living with a serious illness (High confidence). • Screening is undermined by weak health infrastructure. In many settings, a lack of resources results in weak services in competition with other disease control programmes (Moderate confidence). In this context of low investment, people face repeated tests and clinic visits, wasted time, and fraught social interaction with health providers (Moderate confidence). ACF can create expectations for follow-up health care that it cannot deliver (High confidence). Finally, community education improves awareness of tuberculosis in some settings, but lack of full information impacts community members, parents, and health workers, and sometimes leads to harm for children (High confidence). • Health workers are an undervalued but important part of ACF. ACF can feel difficult for health workers in the context of a poorly resourced health system and with people who may not wish to be identified. In addition, the evidence suggests health workers are poorly protected against tuberculosis and fear they or their families might become infected (Moderate confidence). However, they appear to be central to programme success, as the humanity they offer often acts as a driving force for retaining people with tuberculosis in care (Moderate confidence). • Local leadership is necessary but not sufficient for ensuring appropriate programmes. Local leadership creates an intrinsic motivation for communities to value health services (High confidence). However, local leadership cannot guarantee the success of ACF and contact tracing programmes. It is important to balance professional authority with local knowledge and rapport (High confidence). AUTHORS' CONCLUSIONS: Tuberculosis active case finding (ACF) and contact tracing bring a diagnostic service to people who may otherwise not receive it, such as those who are well or without symptoms and those who are sick but who have fewer resources and live further from health facilities. However, capturing these 'missing cases' may in itself be insufficient without appropriate health system strengthening to retain people in care. People who receive a tuberculosis diagnosis must contend with a complex and unsustainable cascade of care, and this affects their perception of ACF and their decision to engage with it.

Indoor residual spraying for preventing malaria in communities using insecticide-treated nets.

BACKGROUND: Insecticide-treated nets (ITNs) and indoor residual spraying (IRS) are used to prevent malaria transmission. Both interventions use insecticides to kill mosquitoes that bite and rest indoors. Adding IRS to ITNs may improve malaria control simply because two interventions can be better than one. Furthermore, IRS may improve malaria control where ITNs are failing due to insecticide resistance. Pyrethroid insecticides are the predominant class of insecticide used for ITNs, as they are more safe than other insecticide classes when in prolonged contact with human skin. While many mosquito populations have developed some resistance to pyrethroid insecticides, a wider range of insecticides can be used for IRS. This review is an update of the previous Cochrane 2019 edition. OBJECTIVES: To summarize the effect on malaria of additionally implementing IRS, using non-pyrethroid-like or pyrethroid-like insecticides, in communities currently using ITNs. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register; CENTRAL; MEDLINE; and five other databases for records from 1 January 2000 to 8 November 2021, on the basis that ITN programmes did not begin to be implemented as policy before the year 2000. SELECTION CRITERIA: We included cluster-randomized controlled trials (cRCTs), interrupted time series (ITS), or controlled before-after studies (CBAs) comparing IRS plus ITNs with ITNs alone. We included studies with at least 50% ITN ownership (defined as the proportion of households owning one or more ITN) in both study arms. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for eligibility, analyzed risk of bias, and extracted data. We used risk ratio (RR) and 95% confidence intervals (CI). We stratified by type of insecticide, 'pyrethroid-like' and 'non-pyrethroid-like'; the latter could improve malaria control better than adding IRS insecticides that have the same way of working as the insecticide on ITNs ('pyrethroid-like'). We used subgroup analysis of ITN usage in the studies to explore heterogeneity. We assessed the certainty of evidence using the GRADE approach. MAIN RESULTS: Eight cRCTs (10 comparisons), one CBA, and one ITS study, all conducted since 2008 in sub-Saharan Africa, met our inclusion criteria. The primary vectors in all sites were mosquitoes belonging to the Anopheles gambiae s.l. complex species; five studies in Benin, Mozambique, Ghana, Sudan, and Tanzania also reported the vector Anopheles funestus. Five cRCTs and both quasi-experimental design studies used insecticides with targets different to pyrethroids (two used bendiocarb, three used pirimiphos-methyl, and one used propoxur. Each of these studies were conducted in areas where the vectors were described as resistant or highly resistant to pyrethroids. Two cRCTs used dichloro-diphenyl-trichlorethane (DDT), an insecticide with the same target as pyrethroids. The remaining cRCT used both types of insecticide (pyrethroid deltamethrin in the first year, switching to bendiocarb for the second year). Indoor residual spraying using 'non-pyrethroid-like' insecticides Six studies were included (four cRCTs, one CBA, and one ITS). Our main analysis for prevalence excluded a study at high risk of bias due to repeated sampling of the same population. This risk did not apply to other outcomes. Overall, the addition of IRS reduced malaria parasite prevalence (RR 0.61, 95% CI 0.42 to 0.88; 4 cRCTs, 16,394 participants; high-certainty evidence). IRS may also reduce malaria incidence on average (rate ratio 0.86, 95% CI 0.61 to 1.23; 4 cRCTs, 323,631 child-years; low-certainty evidence) but the effect was absent in two studies. Subgroup analyses did not explain the qualitative heterogeneity between studies. One cRCT reported no effect on malaria incidence or parasite prevalence in the first year, when a pyrethroid-like insecticide was used for IRS, but showed an effect on both outcomes in the second year, when a non-pyrethroid-like IRS was used. The addition of IRS may also reduce anaemia prevalence (RR 0.71, 95% CI 0.38 to 1.31; 3 cRCTs, 4288 participants; low-certainty evidence). Four cRCTs reported the impact of IRS on entomological inoculation rate (EIR), with variable results; overall, we do not know if IRS had any effect on the EIR in communities using ITNs (very low-certainty evidence). Studies also reported the adult mosquito density and the sporozoite rate, but we could not summarize or pool these entomological outcomes due to differences in the reported data. Three studies measured the prevalence of pyrethroid resistance before and after IRS being introduced: there was no difference detected, but these data are limited. Indoor residual spraying using 'pyrethroid-like' insecticides Adding IRS using a pyrethroid-like insecticide did not appear to markedly alter malaria incidence (rate ratio 1.07, 95% CI 0.80 to 1.43; 2 cRCTs, 15,717 child-years; moderate-certainty evidence), parasite prevalence (RR 1.11, 95% CI 0.86 to 1.44; 3 cRCTs, 10,820 participants; moderate-certainty evidence), or anaemia prevalence (RR 1.12, 95% CI 0.89 to 1.40; 1 cRCT, 4186 participants; low-certainty evidence). Data on EIR were limited so no conclusion was made (very low-certainty evidence). AUTHORS' CONCLUSIONS: in communities using ITNs, the addition of IRS with 'non-pyrethroid-like' insecticides was associated with reduced malaria prevalence. Malaria incidence may also be reduced on average, but there was unexplained qualitative heterogeneity, and the effect may therefore not be observed in all settings. When using 'pyrethroid-like' insecticides, there was no detectable additional benefit of IRS in communities using ITNs.

Repairing boundaries along pathways to tuberculosis case detection: a qualitative synthesis of intervention designs.

BACKGROUND: Tuberculosis case-finding interventions often involve several activities to enhance patient pathways, and it is unclear which activity defines the type of case-finding intervention. When conducting studies to identify the most effective case-finding intervention it is important to have a clear understanding of these interventions for meaningful comparisons. This review aimed to construct a systems-based logic model of all pathways to tuberculosis case detection through a synthesis of intervention designs. METHODS: We identified an existing systematic review on the effectiveness of interventions to increase tuberculosis case detection and updated the search from December 2016 to October 2020. We included randomized controlled trials, as these designs encourage detailed description of interventions. Taking each study in turn, intervention descriptions were read in detail. The texts were analysed qualitatively by constantly comparing emerging codes to construct patient journeys, visualized as logical chains. Actions taken as part of interventions were positioned along patient journeys to theorize the sequence of outcomes. Patient journeys formed the basis of the model, which was refined through discussion. RESULTS: Based on intervention descriptions from 17 randomized controlled trials, our model distinguishes two care-seeking pathways and four screening pathways. An open invitation to people with tuberculosis symptoms creates care-seeking pathways. On care-seeking pathways, systematic screening can be conducted at general health services, but not at specific TB care services. People invited to tuberculosis services regardless of symptoms follow tuberculosis screening pathways and may be identified with presumptive tuberculosis even if they do not seek care for tuberculosis symptoms. Tuberculosis screening pathways include screening offered to all people accessing care at general health services, screening at a mobile clinic or health facility with open invitation to a whole population or tuberculosis contacts, screening personally offered to a whole population or tuberculosis contacts at home, work or school, and screening offered to people receiving care for human immunodeficiency virus or other clinical risk-group care. CONCLUSION: This systems-based logic model of tuberculosis case-finding pathways may support standardized terminology, consistency, transparency and improved communication among researchers, policy-makers, health workers and community members when implementing and evaluating interventions to improve tuberculosis case detection.

Calcium supplementation commencing before or early in pregnancy, for preventing hypertensive disorders of pregnancy.

BACKGROUND: The hypertensive disorders of pregnancy include pre-eclampsia, gestational hypertension, chronic hypertension, and undefined hypertension. Pre-eclampsia is considerably more prevalent in low-income than in high-income countries. One possible explanation for this discrepancy is dietary differences, particularly calcium deficiency. Calcium supplementation in the second half of pregnancy reduces the serious consequences of pre-eclampsia, but has limited effect on the overall risk of pre-eclampsia. It is important to establish whether calcium supplementation before, and in early pregnancy (before 20 weeks' gestation) has added benefit. Such evidence could count towards justification of population-level interventions to improve dietary calcium intake, including fortification of staple foods with calcium, especially in contexts where dietary calcium intake is known to be inadequate. This is an update of a review first published in 2017. OBJECTIVES: To determine the effect of calcium supplementation, given before or early in pregnancy and for at least the first half of pregnancy, on pre-eclampsia and other hypertensive disorders, maternal morbidity and mortality, and fetal and neonatal outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Trials Register (31 July 2018), PubMed (13 July 2018), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP; 31 July 2018), and reference lists of retrieved studies. SELECTION CRITERIA: Eligible studies were randomised controlled trials (RCT) of calcium supplementation, including women not yet pregnant, or women in early pregnancy. Cluster-RCTs, quasi-RCTs, and trials published as abstracts were eligible, but we did not identify any. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data, and checked them for accuracy. They assessed the quality of the evidence for key outcomes using the GRADE approach. MAIN RESULTS: Calcium versus placeboWe included one study (1355 women), which took place across multiple hospital sites in Argentina, South Africa, and Zimbabwe. Most analyses were conducted only on 633 women from this group who were known to have conceived, or on 579 who reached 20 weeks' gestation; the trial was at moderate risk of bias due to high attrition rates pre-conception. Non-pregnant women with previous pre-eclampsia received either calcium 500 mg daily or placebo, from enrolment until 20 weeks' gestation. All participants received calcium 1.5 g daily from 20 weeks until birth.Primary outcomes: calcium supplementation commencing before conception may make little or no difference to the risk of pre-eclampsia (69/296 versus 82/283, risk ratio (RR) 0.80, 95% confidence interval (CI) 0.61 to 1.06; low-quality evidence). For pre-eclampsia or pregnancy loss or stillbirth (or both) at any gestational age, calcium may slightly reduce the risk of this composite outcome, however the 95% CI met the line of no effect (RR 0.82, 95% CI 0.66 to 1.00; low-quality evidence). Supplementation may make little or no difference to the severe maternal morbidity and mortality index (RR 0.93, 95% CI 0.68 to 1.26; low-quality evidence), pregnancy loss or stillbirth at any gestational age (RR 0.83, 95% CI 0.61 to 1,14; low-quality evidence), or caesarean section (RR 1.11, 95% CI 0.96 to 1,28; low-quality evidence).Calcium supplementation may make little or no difference to the following secondary outcomes: birthweight < 2500 g (RR 1.00, 95% CI 0.76 to 1.30; low-quality evidence), preterm birth < 37 weeks (RR 0.90, 95% CI 0.74 to 1.10), early preterm birth < 32 weeks (RR 0.79, 95% CI 0.56 to 1.12), and pregnancy loss, stillbirth or neonatal death before discharge (RR 0.82, 95% CI 0.61 to 1.10; low-quality evidence), no conception, gestational hypertension, gestational proteinuria, severe gestational hypertension, severe pre-eclampsia, severe pre-eclamptic complications index. There was no clear evidence on whether or not calcium might make a difference to perinatal death, or neonatal intensive care unit admission for > 24h, or both (RR 1.11, 95% CI 0.77 to 1.60; low-quality evidence).It is unclear what impact calcium supplementation has on Apgar score < 7 at five minutes (RR 0.43, 95% CI 0.15 to 1.21; very low-quality evidence), stillbirth, early onset pre-eclampsia, eclampsia, placental abruption, intensive care unit admission > 24 hours, maternal death, hospital stay > 7 days from birth, and pregnancy loss before 20 weeks' gestation. AUTHORS' CONCLUSIONS: The single included study suggested that calcium supplementation before and early in pregnancy may reduce the risk of women experiencing the composite outcome pre-eclampsia or pregnancy loss at any gestational age, but the results are inconclusive for all other outcomes for women and babies. Therefore, current evidence neither supports nor refutes the routine use of calcium supplementation before conception and in early pregnancy.To determine the overall benefit of calcium supplementation commenced before or in early pregnancy, the effects found in the study of calcium supplementation limited to the first half of pregnancy need to be added to the known benefits of calcium supplementation in the second half of pregnancy.Further research is needed to confirm whether initiating calcium supplementation pre- or in early pregnancy is associated with a reduction in adverse pregnancy outcomes for mother and baby. Research could also address the acceptability of the intervention to women, which was not covered by this review update.

Interventions during pregnancy to prevent preterm birth: an overview of Cochrane systematic reviews.

BACKGROUND: Preterm birth (PTB) is a major factor contributing to global rates of neonatal death and to longer-term health problems for surviving infants. Both the World Health Organization and the United Nations consider prevention of PTB as central to improving health care for pregnant women and newborn babies. Current preventative clinical strategies show varied efficacy in different populations of pregnant women, frustrating women and health providers alike, while researchers call for better understanding of the underlying mechanisms that lead to PTB. OBJECTIVES: We aimed to summarise all evidence for interventions relevant to the prevention of PTB as reported in Cochrane systematic reviews (SRs). We intended to highlight promising interventions and to identify SRs in need of an update. METHODS: We searched the Cochrane Database of Systematic Reviews (2 November 2017) with key words to capture any Cochrane SR that prespecified or reported a PTB outcome. Inclusion criteria focused on pregnant women without signs of preterm labour or ruptured amniotic membranes. We included reviews of interventions for pregnant women irrespective of their risk status. We followed standard Cochrane methods.We applied GRADE criteria to evaluate the quality of SR evidence. We assigned graphic icons to classify the effectiveness of interventions as: clear evidence of benefit; clear evidence of harm; clear evidence of no effect or equivalence; possible benefit; possible harm; or unknown benefit or harm. We defined clear evidence of benefit and clear evidence of harm to be GRADE moderate- or high-quality evidence with a confidence interval (CI) that does not cross the line of no effect. Clear evidence of no effect or equivalence is GRADE moderate- or high-quality evidence with a narrow CI crossing the line of no effect. Possible benefit and possible harm refer to GRADE low-quality evidence with a clear effect (CI does not cross the line of no effect) or GRADE moderate- or high-quality evidence with a wide CI. Unknown harm or benefit refers to GRADE low- or very low-quality evidence with a wide CI. MAIN RESULTS: We included 83 SRs; 70 had outcome data. Below we highlight key results from a subset of 36 SRs of interventions intended to prevent PTB. OUTCOME: preterm birthClear evidence of benefitFour SRs reported clear evidence of benefit to prevent specific populations of pregnant women from giving birth early, including midwife-led continuity models of care versus other models of care for all women; screening for lower genital tract infections for pregnant women less than 37 weeks' gestation and without signs of labour, bleeding or infection; and zinc supplementation for pregnant women without systemic illness. Cervical cerclage showed clear benefit for women with singleton pregnancy and high risk of PTB only.Clear evidence of harmNo included SR reported clear evidence of harm.No effect or equivalenceFor pregnant women at high risk of PTB, bedrest for women with singleton pregnancy and antibiotic prophylaxis during the second and third trimester were of no effect or equivalent to a comparator.Possible benefitFour SRs found possible benefit in: group antenatal care for all pregnant women; antibiotics for pregnant women with asymptomatic bacteriuria; pharmacological interventions for smoking cessation for pregnant women who smoke; and vitamin D supplements alone for women without pre-existing conditions such as diabetes.Possible harmOne SR reported possible harm (increased risk of PTB) with intramuscular progesterone, but this finding is only relevant to women with multiple pregnancy and high risk of PTB. Another review found possible harm with vitamin D, calcium and other minerals for pregnant women without pre-existing conditions. OUTCOME: perinatal deathClear evidence of benefitTwo SRs reported clear evidence of benefit to reduce pregnant women's risk of perinatal death: midwife-led continuity models of care for all pregnant women; and fetal and umbilical Doppler for high-risk pregnant women.Clear evidence of harmNo included SR reported clear evidence of harm.No effect or equivalenceFor pregnant women at high risk of PTB, antibiotic prophylaxis during the second and third trimester was of no effect or equivalent to a comparator.Possible benefitOne SR reported possible benefit with cervical cerclage for women with singleton pregnancy and high risk of PTB.Possible harmOne SR reported possible harm associated with a reduced schedule of antenatal visits for pregnant women at low risk of pregnancy complications; importantly, these women already received antenatal care in settings with limited resources. OUTCOMES: preterm birth and perinatal deathUnknown benefit or harmFor pregnant women at high risk of PTB for any reason including multiple pregnancy, home uterine monitoring was of unknown benefit or harm. For pregnant women at high risk due to multiple pregnancy: bedrest, prophylactic oral betamimetics, vaginal progesterone and cervical cerclage were all of unknown benefit or harm. AUTHORS' CONCLUSIONS: Implications for practiceThe overview serves as a map and guide to all current evidence relevant to PTB prevention published in the Cochrane Library. Of 70 SRs with outcome data, we identified 36 reviews of interventions with the aim of preventing PTB. Just four of these SRs had evidence of clear benefit to women, with an additional four SRs reporting possible benefit. No SR reported clear harm, which is an important finding for women and health providers alike.The overview summarises no evidence for the clinically important interventions of cervical pessary, cervical length assessment and vaginal progesterone because these Cochrane Reviews were not current. These are active areas for PTB research.The graphic icons we assigned to SR effect estimates do not constitute clinical guidance or an endorsement of specific interventions for pregnant women. It remains critical for pregnant women and their healthcare providers to carefully consider whether specific strategies to prevent PTB will be of benefit for individual women, or for specific populations of women.Implications for researchFormal consensus work is needed to establish standard language for overviews of reviews and to define the limits of their interpretation.Clinicians, researchers and funders must address the lack of evidence for interventions relevant to women at high risk of PTB due to multiple pregnancy.

Cervical stitch (cerclage) for preventing preterm birth in singleton pregnancy.

BACKGROUND: Cervical cerclage is a well-known surgical procedure carried out during pregnancy. It involves positioning of a suture (stitch) around the neck of the womb (cervix), aiming to give mechanical support to the cervix and thereby reduce risk of preterm birth. The effectiveness and safety of this procedure remains controversial. This is an update of a review last published in 2012. OBJECTIVES: To assess whether the use of cervical stitch in singleton pregnancy at high risk of pregnancy loss based on woman's history and/or ultrasound finding of 'short cervix' and/or physical exam improves subsequent obstetric care and fetal outcome. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register (30 June 2016) and reference lists of identified studies. SELECTION CRITERIA: We included all randomised trials of cervical suturing in singleton pregnancies. Cervical stitch was carried out when the pregnancy was considered to be of sufficiently high risk due to a woman's history, a finding of short cervix on ultrasound or other indication determined by physical exam. We included any study that compared cerclage with either no treatment or any alternative intervention. We planned to include cluster-randomised studies but not cross-over trials. We excluded quasi-randomised studies. We included studies reported in abstract form only. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trials for inclusion. Two review authors independently assessed risk of bias and extracted data. We resolved discrepancies by discussion. Data were checked for accuracy. The quality of the evidence was assessed using the GRADE approach. MAIN RESULTS: This updated review includes a total of 15 trials (3490 women); three trials were added for this update (152 women). Cerclage versus no cerclageOverall, cerclage probably leads to a reduced risk of perinatal death when compared with no cerclage, although the confidence interval (CI) crosses the line of no effect (RR 0.82, 95% CI 0.65 to 1.04; 10 studies, 2927 women; moderate quality evidence). Considering stillbirths and neonatal deaths separately reduced the numbers of events and sample size. Although the relative effect of cerclage is similar, estimates were less reliable with fewer data and assessed as of low quality (stillbirths RR 0.89, 95% CI 0.45 to 1.75; 5 studies, 1803 women; low quality evidence; neonatal deaths before discharge RR 0.85, 95% CI 0.53 to 1.39; 6 studies, 1714 women; low quality evidence). Serious neonatal morbidity was similar with and without cerclage (RR 0.80, 95% CI 0.55 to 1.18; 6 studies, 883 women; low-quality evidence). Pregnant women with and without cerclage were equally likely to have a baby discharged home healthy (RR 1.02, 95% CI 0.97 to 1.06; 4 studies, 657 women; moderate quality evidence).Pregnant women with cerclage were less likely to have preterm births compared to controls before 37, 34 (average RR 0.77, 95% CI 0.66 to 0.89; 9 studies, 2415 women; high quality evidence) and 28 completed weeks of gestation.Five subgroups based on clinical indication provided data for analysis (history-indicated; short cervix based on one-off ultrasound in high risk women; short cervix found by serial scans in high risk women; physical exam-indicated; and short cervix found on scan in low risk or mixed populations). There were too few trials in these clinical subgroups to make meaningful conclusions and no evidence of differential effects. Cerclage versus progesteroneTwo trials (129 women) compared cerclage to prevention with vaginal progesterone in high risk women with short cervix on ultrasound; these trials were too small to detect reliable, clinically important differences for any review outcome. One included trial compared cerclage with intramuscular progesterone (75 women) which lacked power to detect group differences. History indicated cerclage versus ultrasound indicated cerclageEvidence from two trials (344 women) was too limited to establish differences for clinically important outcomes. AUTHORS' CONCLUSIONS: Cervical cerclage reduces the risk of preterm birth in women at high-risk of preterm birth and probably reduces risk of perinatal deaths. There was no evidence of any differential effect of cerclage based on previous obstetric history or short cervix indications, but data were limited for all clinical groups. The question of whether cerclage is more or less effective than other preventative treatments, particularly vaginal progesterone, remains unanswered.

Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth.

BACKGROUND: Respiratory morbidity including respiratory distress syndrome (RDS) is a serious complication of preterm birth and the primary cause of early neonatal mortality and disability. While researching the effects of the steroid dexamethasone on premature parturition in fetal sheep in 1969, Liggins found that there was some inflation of the lungs of lambs born at gestations at which the lungs would be expected to be airless. Liggins and Howie published the first randomised controlled trial in humans in 1972 and many others followed. OBJECTIVES: To assess the effects of administering a course of corticosteroids to the mother prior to anticipated preterm birth on fetal and neonatal morbidity and mortality, maternal mortality and morbidity, and on the child in later life. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register (17 February 2016) and reference lists of retrieved studies. SELECTION CRITERIA: We considered all randomised controlled comparisons of antenatal corticosteroid administration (betamethasone, dexamethasone, or hydrocortisone) with placebo, or with no treatment, given to women with a singleton or multiple pregnancy, prior to anticipated preterm delivery (elective, or following spontaneous labour), regardless of other co-morbidity, for inclusion in this review. Most women in this review received a single course of steroids; however, nine of the included trials allowed for women to have weekly repeats. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. The quality of the evidence was assessed using the GRADE approach. MAIN RESULTS: This update includes 30 studies (7774 women and 8158 infants). Most studies are of low or unclear risk for most bias domains. An assessment of high risk usually meant a trial had potential for performance bias due to lack of blinding. Two trials had low risks of bias for all risk of bias domains.Treatment with antenatal corticosteroids (compared with placebo or no treatment) is associated with a reduction in the most serious adverse outcomes related to prematurity, including: perinatal death (average risk ratio (RR) 0.72, 95% confidence interval (CI) 0.58 to 0.89; participants = 6729; studies = 15; Tau² = 0.05, I² = 34%; moderate-quality); neonatal death (RR 0.69, 95% CI 0.59 to 0.81; participants = 7188; studies = 22), RDS (average RR 0.66, 95% CI 0.56 to 0.77; participants = 7764; studies = 28; Tau² = 0.06, I² = 48%; moderate-quality); moderate/severe RDS (average RR 0.59, 95% CI 0.38 to 0.91; participants = 1686; studies = 6; Tau² = 0.14, I² = 52%); intraventricular haemorrhage (IVH) (average RR 0.55, 95% CI 0.40 to 0.76; participants = 6093; studies = 16; Tau² = 0.10, I² = 33%; moderate-quality), necrotising enterocolitis (RR 0.50, 95% CI 0.32 to 0.78; participants = 4702; studies = 10); need for mechanical ventilation (RR 0.68, 95% CI 0.56 to 0.84; participants = 1368; studies = 9); and systemic infections in the first 48 hours of life (RR 0.60, 95% CI 0.41 to 0.88; participants = 1753; studies = 8).There was no obvious benefit for: chronic lung disease (average RR 0.86, 95% CI 0.42 to 1.79; participants = 818; studies = 6; Tau² = 0.38 I² = 65%); mean birthweight (g) (MD -18.47, 95% CI -40.83 to 3.90; participants = 6182; studies = 16; moderate-quality); death in childhood (RR 0.68, 95% CI 0.36 to 1.27; participants = 1010; studies = 4); neurodevelopment delay in childhood (RR 0.64, 95% CI 0.14 to 2.98; participants = 82; studies = 1); or death into adulthood (RR 1.00, 95% CI 0.56 to 1.81; participants = 988; studies = 1).Treatment with antenatal corticosteroids does not increase the risk of chorioamnionitis (RR 0.83, 95% CI 0.66 to 1.06; participants = 5546; studies = 15; moderate-quality evidence) or endometritis (RR 1.20, 95% CI 0.87 to 1.63; participants = 4030; studies = 10; Tau² = 0.11, I² = 28%; moderate-quality). No increased risk in maternal death was observed. However, the data on maternal death is based on data from a single trial with two deaths; four other trials reporting maternal death had zero events (participants = 3392; studies = 5; moderate-quality).There is no definitive evidence to suggest that antenatal corticosteroids work differently in any pre-specified subgroups (singleton versus multiple pregnancy; membrane status; presence of hypertension) or for different study protocols (type of corticosteroid; single course or weekly repeats).GRADE outcomes were downgraded to moderate-quality. Downgrading decisions (for perinatal death, RDS, IVH, and mean birthweight) were due to limitations in study design or concerns regarding precision (chorioamnionitis, endometritis). Maternal death was downgraded for imprecision due to few events. AUTHORS' CONCLUSIONS: Evidence from this update supports the continued use of a single course of antenatal corticosteroids to accelerate fetal lung maturation in women at risk of preterm birth. A single course of antenatal corticosteroids could be considered routine for preterm delivery. It is important to note that most of the evidence comes from high income countries and hospital settings; therefore, the results may not be applicable to low-resource settings with high rates of infections.There is little need for further trials of a single course of antenatal corticosteroids versus placebo in singleton pregnancies in higher income countries and hospital settings. However, data are sparse in lower income settings. There are also few data regarding risks and benefits of antenatal corticosteroids in multiple pregnancies and other high-risk obstetric groups. Further information is also required concerning the optimal dose-to-delivery interval, and the optimal corticosteroid to use.We encourage authors of previous studies to provide further information, which may answer any remaining questions about the use of antenatal corticosteroids in such pregnancies without the need for further randomised controlled trials. Individual patient data meta-analysis from published trials is likely to answer some of the evidence gaps. Follow-up studies into childhood and adulthood, particularly in the late preterm gestation and repeat courses groups, are needed. We have not examined the possible harmful effects of antenatal corticosteroids in low-resource settings in this review. It would be particularly relevant to explore this finding in adequately powered prospective trials.

Early skin-to-skin contact for mothers and their healthy newborn infants.

BACKGROUND: Mother-infant separation post birth is common. In standard hospital care, newborn infants are held wrapped or dressed in their mother's arms, placed in open cribs or under radiant warmers. Skin-to-skin contact (SSC) begins ideally at birth and should last continually until the end of the first breastfeeding. SSC involves placing the dried, naked baby prone on the mother's bare chest, often covered with a warm blanket. According to mammalian neuroscience, the intimate contact inherent in this place (habitat) evokes neuro-behaviors ensuring fulfillment of basic biological needs. This time frame immediately post birth may represent a 'sensitive period' for programming future physiology and behavior. OBJECTIVES: To assess the effects of immediate or early SSC for healthy newborn infants compared to standard contact on establishment and maintenance of breastfeeding and infant physiology. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (17 December 2015), made personal contact with trialists, consulted the bibliography on kangaroo mother care (KMC) maintained by Dr Susan Ludington, and reviewed reference lists of retrieved studies. SELECTION CRITERIA: Randomized controlled trials that compared immediate or early SSC with usual hospital care. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Quality of the evidence was assessed using the GRADE approach. MAIN RESULTS: We included 46 trials with 3850 women and their infants; 38 trials with 3472 women and infants contributed data to our analyses. Trials took place in 21 countries, and most recruited small samples (just 12 trials randomized more than 100 women). Eight trials included women who had SSC after cesarean birth. All infants recruited to trials were healthy, and the majority were full term. Six trials studied late preterm infants (greater than 35 weeks' gestation). No included trial met all criteria for good quality with respect to methodology and reporting; no trial was successfully blinded, and all analyses were imprecise due to small sample size. Many analyses had statistical heterogeneity due to considerable differences between SSC and standard care control groups. Results for womenSSC women were more likely than women with standard contact to be breastfeeding at one to four months post birth, though there was some uncertainty in this estimate due to risks of bias in included trials (average risk ratio (RR) 1.24, 95% confidence interval (CI) 1.07 to 1.43; participants = 887; studies = 14; I² = 41%; GRADE: moderate quality). SSC women also breast fed their infants longer, though data were limited (mean difference (MD) 64 days, 95% CI 37.96 to 89.50; participants = 264; studies = six; GRADE:low quality); this result was from a sensitivity analysis excluding one trial contributing all of the heterogeneity in the primary analysis. SSC women were probably more likely to exclusively breast feed from hospital discharge to one month post birth and from six weeks to six months post birth, though both analyses had substantial heterogeneity (from discharge average RR 1.30, 95% CI 1.12 to 1.49; participants = 711; studies = six; I² = 44%; GRADE: moderate quality; from six weeks average RR 1.50, 95% CI 1.18 to 1.90; participants = 640; studies = seven; I² = 62%; GRADE: moderate quality).Women in the SCC group had higher mean scores for breastfeeding effectiveness, with moderate heterogeneity (IBFAT (Infant Breastfeeding Assessment Tool) score MD 2.28, 95% CI 1.41 to 3.15; participants = 384; studies = four; I² = 41%). SSC infants were more likely to breast feed successfully during their first feed, with high heterogeneity (average RR 1.32, 95% CI 1.04 to 1.67; participants = 575; studies = five; I² = 85%). Results for infantsSSC infants had higher SCRIP (stability of the cardio-respiratory system) scores overall, suggesting better stabilization on three physiological parameters. However, there were few infants, and the clinical significance of the test was unclear because trialists reported averages of multiple time points (standardized mean difference (SMD) 1.24, 95% CI 0.76 to 1.72; participants = 81; studies = two; GRADE low quality). SSC infants had higher blood glucose levels (MD 10.49, 95% CI 8.39 to 12.59; participants = 144; studies = three; GRADE: low quality), but similar temperature to infants in standard care (MD 0.30 degree Celcius (°C) 95% CI 0.13 °C to 0.47 °C; participants = 558; studies = six; I² = 88%; GRADE: low quality). Women and infants after cesarean birthWomen practicing SSC after cesarean birth were probably more likely to breast feed one to four months post birth and to breast feed successfully (IBFAT score), but analyses were based on just two trials and few women. Evidence was insufficient to determine whether SSC could improve breastfeeding at other times after cesarean. Single trials contributed to infant respiratory rate, maternal pain and maternal state anxiety with no power to detect group differences. SubgroupsWe found no differences for any outcome when we compared times of initiation (immediate less than 10 minutes post birth versus early 10 minutes or more post birth) or lengths of contact time (60 minutes or less contact versus more than 60 minutes contact). AUTHORS' CONCLUSIONS: Evidence supports the use of SSC to promote breastfeeding. Studies with larger sample sizes are necessary to confirm physiological benefit for infants during transition to extra-uterine life and to establish possible dose-response effects and optimal initiation time. Methodological quality of trials remains problematic, and small trials reporting different outcomes with different scales and limited data limit our confidence in the benefits of SSC for infants. Our review included only healthy infants, which limits the range of physiological parameters observed and makes their interpretation difficult.

Fetal and umbilical Doppler ultrasound in normal pregnancy.

BACKGROUND: One of the main aims of routine antenatal care is to identify the 'at risk' fetus in order to apply clinical interventions which could result in reduced perinatal morbidity and mortality. Doppler ultrasound study of umbilical artery waveforms helps to identify the compromised fetus in 'high-risk' pregnancies and, therefore, deserves assessment as a screening test in 'low-risk' pregnancies. OBJECTIVES: To assess the effects on obstetric practice and pregnancy outcome of routine fetal and umbilical Doppler ultrasound in unselected and low-risk pregnancies. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (28 February 2015) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of Doppler ultrasound for the investigation of umbilical and fetal vessels waveforms in unselected pregnancies compared with no Doppler ultrasound. Studies where uterine vessels have been assessed together with fetal and umbilical vessels have been included. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. In addition to standard meta-analysis, the two primary outcomes and five of the secondary outcomes were assessed using GRADE software and methodology. MAIN RESULTS: We included five trials that recruited 14,624 women, with data analysed for 14,185 women. All trials had adequate allocation concealment, but none had adequate blinding of participants, staff or outcome assessors. Overall and apart from lack of blinding, the risk of bias for the included trials was considered to be low.Overall, routine fetal and umbilical Doppler ultrasound examination in low-risk or unselected populations did not result in increased antenatal, obstetric and neonatal interventions. There were no group differences noted for the review's primary outcomes of perinatal death and neonatal morbidity. Results for perinatal death were as follows: (average risk ratio (RR) 0.80, 95% confidence interval (CI) 0.35 to 1.83; four studies, 11,183 participants). Only one included trial assessed serious neonatal morbidity and found no evidence of group differences (RR 0.99, 95% CI 0.06 to 15.75; one study, 2016 participants).For the comparison of a single Doppler assessment versus no Doppler, evidence for group differences in perinatal death was detected (RR 0.36, 95% CI 0.13 to 0.99; one study, 3891 participants). However, these results are based on a single trial, and we would recommend caution when interpreting this finding.There was no evidence of group differences for the outcomes of caesarean section, neonatal intensive care admissions or preterm birth less than 37 weeks.When the quality of the evidence for the main comparison of 'All Doppler versus no Doppler' was assessed with GRADE software, the outcomes of perinatal death and serious neonatal morbidity data were graded as of low quality. Evidence for the outcome of stillbirth was graded according to regimen subgroups - with a moderate quality rating for stillbirth (fetal/umbilical vessels only) and a low quality rating for stillbirth (fetal/umbilical vessels + uterine artery vessels). Evidence for admission to neonatal intensive care unit was assessed as of moderate quality, and evidence for the outcomes of caesarean section and preterm birth less than 37 weeks was graded as of high quality.There is no available evidence to assess the effect on substantive long-term outcomes such as childhood neurodevelopment and no data to assess maternal outcomes, particularly maternal satisfaction. AUTHORS' CONCLUSIONS: Existing evidence does not provide conclusive evidence that the use of routine umbilical artery Doppler ultrasound, or combination of umbilical and uterine artery Doppler ultrasound in low-risk or unselected populations benefits either mother or baby. Future studies should be designed to address small changes in perinatal outcome, and should focus on potentially preventable deaths.

Different strategies for diagnosing gestational diabetes to improve maternal and infant health.

BACKGROUND: Gestational diabetes mellitus (GDM) is carbohydrate intolerance resulting in hyperglycaemia with onset or first recognition during pregnancy. If untreated, perinatal morbidity and mortality may be increased. Accurate diagnosis allows appropriate treatment. Use of different tests and different criteria will influence which women are diagnosed with GDM. OBJECTIVES: To evaluate and compare different testing strategies for diagnosis of gestational diabetes mellitus to improve maternal and infant health while assessing their impact on healthcare service costs. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2014) and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised trials if they evaluated tests carried out to diagnose GDM. We excluded studies that used a quasi-random model. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: We identified six small trials, including 694 women. These trials were assessed as having varying risk of bias, with few outcomes reported. We prespecified six outcomes to be assessed for quality using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach; data for only one outcome (diagnosis of gestational diabetes) were available for assessment. One trial compared three different methods of delivering glucose: a candy bar (39 women), a 50-gram glucose polymer drink (40 women) and a 50-gram glucose monomer drink (43 women). We have reported results reported by this trial as separate comparisons. 75-gram oral glucose tolerance test (OGTT) versus 100-gram OGTT (one trial, 248 women): Women given the 75-gram OGTT had a higher relative risk of being diagnosed with GDM (risk ratio (RR) 2.55, 95% confidence interval (CI) 0.96 to 6.75). This difference was borderline in terms of statistical significance, and evidence was considered to be of very low quality when assessed by GRADE. No data were reported for the following additional outcomes prespecified for assessment in GRADE: caesarean section, macrosomia > 4.5 kg or however defined in the trial, long-term type 2 diabetes maternal, long-term type 2 diabetes infant and economic costs. Candy bar versus 50-gram glucose monomer drink (one trial, 60 women): More women receiving the candy bar, rather than glucose monomer, preferred the taste of the candy bar (RR 0.60, 95% CI 0.42 to 0.86). Infant outcomes were not reported. 50-gram glucose polymer drink versus 50-gram glucose monomer drink (three trials, 239 women): Mean difference (MD) in gestation at birth was -0.80 weeks (one trial, 100 women; 95% CI -1.69 to 0.09). Total side effects were less common with the glucose polymer drink (one trial, 63 women; RR 0.21, 95% CI 0.07 to 0.59), and no clear difference in taste acceptability was reported (one trial, 63 women; RR 0.99, 95% CI 0.76 to 1.29). Significantly fewer women reported nausea following the 50-gram glucose polymer drink compared with the 50-gram glucose monomer drink (one trial, 66 women; RR 0.29, 95% CI 0.11 to 0.78). No other measures of maternal morbidity or outcomes for the infant were reported. 50-gram glucose food versus 50-gram glucose drink (one trial, 30 women): Women receiving glucose in their food, rather than as a drink, reported fewer side effects (RR 0.08, 95% CI 0.01 to 0.56). No clear difference was noted in the number of women requiring further testing (RR 0.14, 95% CI 0.01 to 2.55). No other measures of maternal morbidity or outcome were reported for the infant. 75-gram oral glucose tolerance test (OGTT) World Health Organization (WHO) criteria versus 75-gram OGTT American Diabetes Association (ADA) criteria (one trial, 116 women): No clear differences in included outcomes were observed between women who received the 75-gram OGTT and were diagnosed using criteria based on WHO (1999) recommendations and women who received the 75-gram OGTT and were diagnosed using criteria recommended by the ADA (1979). Outcomes measured included diagnosis of gestational diabetes (RR 1.47, 95% CI 0.66 to 3.25), caesarean birth (RR 1.07, 95% CI 0.85 to 1.35), macrosomia defined as > 90th percentile by ultrasound or birthweight equal to or exceeding 4000 g (RR 0.73, 95% CI 0.19 to 2.79), stillbirth (RR 0.49, 95% CI 0.02 to 11.68) and instrumental birth (RR 0.21, 95% CI 0.01 to 3.94). AUTHORS' CONCLUSIONS: Evidence is insufficient to permit assessment of which strategy is best for diagnosing GDM.

Routine ultrasound in late pregnancy (after 24 weeks' gestation).

BACKGROUND: Diagnostic ultrasound is used selectively in late pregnancy where there are specific clinical indications. However, the value of routine late pregnancy ultrasound screening in unselected populations is controversial. The rationale for such screening would be the detection of clinical conditions which place the fetus or mother at high risk, which would not necessarily have been detected by other means such as clinical examination, and for which subsequent management would improve perinatal outcome. OBJECTIVES: To assess the effects on obstetric practice and pregnancy outcome of routine late pregnancy ultrasound, defined as greater than 24 weeks' gestation, in women with either unselected or low-risk pregnancies. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2015) and reference lists of retrieved studies. SELECTION CRITERIA: All acceptably controlled trials of routine ultrasound in late pregnancy (defined as after 24 weeks). DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: Thirteen trials recruiting 34,980 women were included in the systematic review. Risk of bias was low for allocation concealment and selective reporting, unclear for random sequence generation and incomplete outcome data and high for blinding of both outcome assessment and participants and personnel. There was no difference in antenatal, obstetric and neonatal outcome or morbidity in screened versus control groups. Routine late pregnancy ultrasound was not associated with improvements in overall perinatal mortality. There is little information on long-term substantive outcomes such as neurodevelopment. There is a lack of data on maternal psychological effects.Overall, the evidence for the primary outcomes of perinatal mortality, preterm birth less than 37 weeks, induction of labour and caesarean section were assessed to be of moderate or high quality with GRADE software. There was no association between ultrasound in late pregnancy and perinatal mortality (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.67 to 1.54; participants = 30,675; studies = eight; I² = 29%), preterm birth less than 37 weeks (RR 0.96, 95% CI 0.85 to 1.08; participants = 17,151; studies = two; I² = 0%), induction of labour (RR 0.93, 95% CI 0.81 to 1.07; participants = 22,663; studies = six; I² = 78%), or caesarean section (RR 1.03, 95% CI 0.92 to 1.15; participants = 27,461; studies = six; I² = 54%). Three additional primary outcomes chosen for the 'Summary of findings' table were preterm birth less than 34 weeks, maternal psychological effects and neurodevelopment at age two. Because none of the included studies reported these outcomes, they were not assessed for quality with GRADE software. AUTHORS' CONCLUSIONS: Based on existing evidence, routine late pregnancy ultrasound in low-risk or unselected populations does not confer benefit on mother or baby. There was no difference in the primary outcomes of perinatal mortality, preterm birth less than 37 weeks, caesarean section rates, and induction of labour rates if ultrasound in late pregnancy was performed routinely versus not performed routinely. Meanwhile, data were lacking for the other primary outcomes: preterm birth less than 34 weeks, maternal psychological effects, and neurodevelopment at age two, reflecting a paucity of research covering these outcomes. These outcomes may warrant future research.

Calcium supplementation (other than for preventing or treating hypertension) for improving pregnancy and infant outcomes.

BACKGROUND: Maternal nutrition during pregnancy is known to have an effect on fetal growth and development. It is recommended that women increase their calcium intake during pregnancy and lactation, although the recommended dosage varies among professionals. Currently, there is no consensus on the role of routine calcium supplementation for pregnant women other than for preventing or treating hypertension. OBJECTIVES: To determine the effect of calcium supplementation on maternal, fetal and neonatal outcomes (other than for preventing or treating hypertension) as well as any possible side effects. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30th September 2014). SELECTION CRITERIA: We considered all published, unpublished and ongoing randomised controlled trials (RCTs) comparing maternal, fetal and neonatal outcomes in pregnant women who received calcium supplementation versus placebo or no treatment. Cluster-RCTs were eligible for inclusion but none were identified. Quasi-RCTs and cross-over studies were not eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: Twenty-five studies met the inclusion criteria, but only 23 studies contributed data to the review. These 23 trials recruited 18,587 women, with 17,842 women included in final analyses. There were no statistically significant differences between women who received calcium supplementation and those who did not in terms of reducing preterm births less than 37 weeks' gestation (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.70 to 1.05; 13 studies, 16,139 women; random-effects model) or less than 34 weeks' gestation (RR 1.04, 95% CI 0.80 to 1.36; four trials, 5669). Most studies were of low risk of bias. We conducted sensitivity analysis for the outcome of preterm birth less than 37 weeks by removing two trials with unclear risk of bias for allocation concealment; the results then favoured treatment with calcium supplementation (RR 0.80, 95% CI 0.65 to 0.99; 11 trials, 15,379 women). There was no significant difference in infant low birthweight between the two treatment groups (RR 0.93, 95% CI 0.81 to 1.07; six trials, 14,162 infants; random-effects model). However, when compared to the control group, women in the calcium supplementation group gave birth to slightly heavier birthweight infants (mean difference 56.40, 95% CI 13.55 to 99.25; 21 trials, 9202 women; random-effects model).Three outcomes were chosen for assessment with the GRADE software: preterm birth less than 37 weeks; preterm birth less than 34 weeks; and low birthweight less than 2500 g. Evidence for these outcomes was assessed as of moderate quality. AUTHORS' CONCLUSIONS: This review indicates that there are no clear additional benefits to calcium supplementation in prevention of preterm birth or low infant birthweight. While there was a statistically significant difference of 56 g identified in mean infant birthweight, there was significant heterogeneity identified, and the clinical significance of this difference is uncertain.

Health system and community level interventions for improving antenatal care coverage and health outcomes.

BACKGROUND: The World Health Organization (WHO) recommends at least four antenatal care (ANC) visits for all pregnant women. Almost half of pregnant women worldwide, and especially in developing countries do not receive this amount of care. Poor attendance of ANC is associated with delivery of low birthweight babies and more neonatal deaths. ANC may include education on nutrition, potential problems with pregnancy or childbirth, child care and prevention or detection of disease during pregnancy.This review focused on community-based interventions and health systems-related interventions. OBJECTIVES: To assess the effects of health system and community interventions for improving coverage of antenatal care and other perinatal health outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (7 June 2015) and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs), quasi-randomised trials and cluster-randomised trials. Trials of any interventions to improve ANC coverage were eligible for inclusion. Trials were also eligible if they targeted specific and related outcomes, such as maternal or perinatal death, but also reported ANC coverage. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: We included 34 trials involving approximately 400,000 women. Some trials tested community-based interventions to improve uptake of antenatal care (media campaigns, education or financial incentives for pregnant women), while other trials looked at health systems interventions (home visits for pregnant women or equipment for clinics). Most trials took place in low- and middle-income countries, and 29 of the 34 trials used a cluster-randomised design. We assessed 30 of the 34 trials as of low or unclear overall risk of bias. Comparison 1: One intervention versus no interventionWe found marginal improvements in ANC coverage of at least four visits (average odds ratio (OR) 1.11, 95% confidence interval (CI) 1.01 to 1.22; participants = 45,022; studies = 10; Heterogeneity: Tau² = 0.01; I² = 52%; high quality evidence). Sensitivity analysis with a more conservative intra-cluster correlation co-efficient (ICC) gave similar marginal results. Excluding one study at high risk of bias shifted the marginal pooled estimate towards no effect. There was no effect on pregnancy-related deaths (average OR 0.69, 95% CI 0.45 to 1.08; participants = 114,930; studies = 10; Heterogeneity: Tau² = 0.00; I² = 0%; low quality evidence), perinatal mortality (average OR 0.98, 95% CI 0.90 to 1.07; studies = 15; Heterogeneity: Tau² = 0.01; I² = 58%; moderate quality evidence) or low birthweight (average OR 0.94, 95% CI 0.82 to 1.06; studies = five; Heterogeneity: Tau² = 0.00; I² = 5%; high quality evidence). Single interventions led to marginal improvements in the number of women who delivered in health facilities (average OR 1.08, 95% CI 1.02 to 1.15; studies = 10; Heterogeneity: Tau² = 0.00; I² = 0%; high quality evidence), and in the proportion of women who had at least one ANC visit (average OR 1.68, 95% CI 1.02 to 2.79; studies = six; Heterogeneity: Tau² = 0.24; I² = 76%; moderate quality evidence). Results for ANC coverage (at least four and at least one visit) and for perinatal mortality had substantial statistical heterogeneity. Single interventions did not improve the proportion of women receiving tetanus protection (average OR 1.03, 95% CI 0.92 to 1.15; studies = 8; Heterogeneity: Tau² = 0.01; I² = 57%). No study reported onintermittent prophylactic treatment for malaria. Comparison 2: Two or more interventions versus no interventionWe found no improvements in ANC coverage of four or more visits (average OR 1.48, 95% CI 0.99 to 2.21; participants = 7840; studies = six; Heterogeneity: Tau² = 0.10; I² = 48%; low quality evidence) or pregnancy-related deaths (average OR 0.70, 95% CI 0.39 to 1.26; participants = 13,756; studies = three; Heterogeneity: Tau² = 0.00; I² = 0%; moderate quality evidence). However, combined interventions led to improvements in ANC coverage of at least one visit (average OR 1.79, 95% CI 1.47 to 2.17; studies = five; Heterogeneity: Tau² = 0.00; I² = 0%; moderate quality evidence), perinatal mortality (average OR 0.74, 95% CI 0.57 to 0.95; studies = five; Heterogeneity: Tau² = 0.06; I² = 83%; moderate quality evidence) and low birthweight (average OR 0.61, 95% CI 0.46 to 0.80; studies = two; Heterogeneity: Tau² = 0.00; I² = 0%; moderate quality evidence). Meta-analyses for both ANC coverage four or more visits and perinatal mortality had substantial statistical heterogeneity. Combined interventions improved the proportion of women who had tetanus protection (average OR 1.48, 95% CI 1.18 to 1.87; studies = 3; Heterogeneity: Tau² = 0.01; I² = 33%). No trial in this comparison reported on intermittent prophylactic treatment for malaria. Comparison 3: Two interventions compared head to head. No trials found. Comparison 4: One intervention versus a combination of interventionsThere was no difference in ANC coverage (four or more visits and at least one visit), pregnancy-related deaths, deliveries in a health facility or perinatal mortality. No trials in this comparison reported on low birthweight orintermittent prophylactic treatment of malaria. AUTHORS' CONCLUSIONS: Implications for practice - Single interventions may improve ANC coverage (at least one visit and four or more visits) and deliveries in health facilities. Combined interventions may improve ANC coverage (at least one visit), reduce perinatal mortality and reduce the occurrence of low birthweight. The effects of the interventions are unrelated to whether they are community or health system interventions. Implications for research - More details should be provided in reporting numbers of events, group totals and the ICCs used to adjust for cluster effects. Outcomes should be reported uniformly so that they are comparable to commonly-used population indicators. We recommend further cluster-RCTs of pregnant women and women in their reproductive years, using combinations of interventions and looking at outcomes that are important to pregnant women, such as maternal and perinatal morbidity and mortality, alongside the explanatory outcomes along the pathway of care: ANC coverage, the services provided during ANC and deliveries in health facilities.

Group versus conventional antenatal care for women.

BACKGROUND: Antenatal care is one of the key preventive health services used around the world. In most Western countries, antenatal care traditionally involves a schedule of one-to-one visits with a care provider. A different way of providing antenatal care involves use of a group model. OBJECTIVES: 1. To compare the effects of group antenatal care versus conventional antenatal care on psychosocial, physiological, labour and birth outcomes for women and their babies.2. To compare the effects of group antenatal care versus conventional antenatal care on care provider satisfaction. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2014), contacted experts in the field and reviewed the reference lists of retrieved studies. SELECTION CRITERIA: All identified published, unpublished and ongoing randomised and quasi-randomised controlled trials comparing group antenatal care with conventional antenatal care were included. Cluster-randomised trials were eligible, and one has been included. Cross-over trials were not eligible. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias and extracted data; all review authors checked data for accuracy. MAIN RESULTS: We included four studies (2350 women). The overall risk of bias for the included studies was assessed as acceptable in two studies and good in two studies. No statistically significant differences were observed between women who received group antenatal care and those given standard individual antenatal care for the primary outcome of preterm birth (risk ratio (RR) 0.75, 95% confidence interval (CI) 0.57 to 1.00; three trials; N = 1888). The proportion of low-birthweight (less than 2500 g) babies was similar between groups (RR 0.92, 95% CI 0.68 to 1.23; three trials; N = 1935). No group differences were noted for the primary outcomes small-for-gestational age (RR 0.92, 95% CI 0.68 to 1.24; two trials; N = 1473) and perinatal mortality (RR 0.63, 95% CI 0.32 to 1.25; three trials; N = 1943).Satisfaction was rated as high among women who were allocated to group antenatal care, but this outcome was measured in only one trial. In this trial, mean satisfaction with care in the group given antenatal care was almost five times greater than that reported by those allocated to standard care (mean difference 4.90, 95% CI 3.10 to 6.70; one study; N = 993). No differences in neonatal intensive care admission, initiation of breastfeeding or spontaneous vaginal birth were observed between groups. Several outcomes related to stress and depression were reported in one trial. No differences between groups were observed for any of these outcomes.No data were available on the effects of group antenatal care on care provider satisfaction.We used the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach to assess evidence for seven prespecified outcomes; results ranged from low quality (perinatal mortality) to moderate quality (preterm birth, low birthweight, neonatal intensive care unit admission, breastfeeding initiation) to high quality (satisfaction with antenatal care, spontaneous vaginal birth). AUTHORS' CONCLUSIONS: Available evidence suggests that group antenatal care is positively viewed by women and is associated with no adverse outcomes for them or for their babies. No differences in the rate of preterm birth were reported when women received group antenatal care. This review is limited because of the small numbers of studies and women, and because one study contributed 42% of the women. Most of the analyses are based on a single study. Additional research is required to determine whether group antenatal care is associated with significant benefit in terms of preterm birth or birthweight.

Interventions for preventing or reducing domestic violence against pregnant women.

BACKGROUND: Domestic violence during pregnancy is a major public health concern. This preventable risk factor threatens both the mother and baby. Routine perinatal care visits offer opportunities for healthcare professionals to screen and refer abused women for effective interventions. It is, however, not clear which interventions best serve mothers during pregnancy and postpartum to ensure their safety. OBJECTIVES: To examine the effectiveness and safety of interventions in preventing or reducing domestic violence against pregnant women. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 July 2014), scanned bibliographies of published studies and corresponded with investigators. SELECTION CRITERIA: We included randomised controlled trials (RCTs) including cluster-randomised trials, and quasi-randomised controlled trials (e.g. where there was alternate allocation) investigating the effect of interventions in preventing or reducing domestic violence during pregnancy. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: We included 10 trials with a total of 3417 women randomised. Seven of these trials, recruiting 2629 women, contributed data to the review. However, results for all outcomes were based on single studies. There was limited evidence for the primary outcomes of reduction of episodes of violence (physical, sexual, and/or psychological) and prevention of violence during and up to one year after pregnancy (as defined by the authors of trials). In one study, women who received the intervention reported fewer episodes of partner violence during pregnancy and in the postpartum period (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.43 to 0.88, 306 women, moderate quality). Groups did not differ for Conflict Tactics Score - the mean partner abuse scores in the first three months postpartum (mean difference (MD) 4.20 higher, 95% CI -10.74 to 19.14, one study, 46 women, very low quality). The Current Abuse Score for partner abuse in the first three months was also similar between groups (MD -0.12 lower, 95% CI -0.31 lower to 0.07 higher, one study, 191 women, very low quality). Evidence for the outcomes episodes of partner abuse during pregnancy or episodes during the first three months postpartum was not significant (respectively, RR 0.50, 95% CI 0.25 to 1.02, one study with 220 women, very low quality; and RR 0.60, 95% CI 0.35 to 1.04, one study, 271 women, very low quality). Finally, the risk for low birthweight (< 2500 g) did not differ between groups (RR 0.74, 95 % CI 0.41 to 1.32, 306 infants, low quality).There were few statistically significant differences between intervention and control groups for depression during pregnancy and the postnatal period. Only one study reported findings for neonatal outcomes such as preterm delivery and birthweight, and there were no clinically significant differences between groups. None of the studies reported results for other secondary outcomes: Apgar score less than seven at one minute and five minutes, stillbirth, neonatal death, miscarriage, maternal mortality, antepartum haemorrhage, and placental abruption. AUTHORS' CONCLUSIONS: There is insufficient evidence to assess the effectiveness of interventions for domestic violence on pregnancy outcomes. There is a need for high-quality, RCTs with adequate statistical power to determine whether intervention programs prevent or reduce domestic violence episodes during pregnancy, or have any effect on maternal and neonatal mortality and morbidity outcomes.

Interventions to prevent spontaneous preterm birth in women with singleton pregnancy who are at high risk: systematic review and network meta-analysis.

OBJECTIVES: To compare the efficacy of bed rest, cervical cerclage (McDonald, Shirodkar, or unspecified type of cerclage), cervical pessary, fish oils or omega fatty acids, nutritional supplements (zinc), progesterone (intramuscular, oral, or vaginal), prophylactic antibiotics, prophylactic tocolytics, combinations of interventions, placebo or no treatment (control) to prevent spontaneous preterm birth in women with a singleton pregnancy and a history of spontaneous preterm birth or short cervical length. DESIGN: Systematic review with bayesian network meta-analysis. DATA SOURCES: The Cochrane Pregnancy and Childbirth Group's Database of Trials, the Cochrane Central Register of Controlled Trials, Medline, Embase, CINAHL, relevant journals, conference proceedings, and registries of ongoing trials. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials of pregnant women who are at high risk of spontaneous preterm birth because of a history of spontaneous preterm birth or short cervical length. No language or date restrictions were applied. OUTCOMES: Seven maternal outcomes and 11 fetal outcomes were analysed in line with published core outcomes for preterm birth research. Relative treatment effects (odds ratios and 95% credible intervals) and certainty of evidence are presented for outcomes of preterm birth <34 weeks and perinatal death. RESULTS: Sixty one trials (17 273 pregnant women) contributed data for the analysis of at least one outcome. For preterm birth <34 weeks (40 trials, 13 310 pregnant women) and with placebo or no treatment as the comparator, vaginal progesterone was associated with fewer women with preterm birth <34 weeks (odds ratio 0.50, 95% credible interval 0.34 to 0.70, high certainty of evidence). Shirodkar cerclage showed the largest effect size (0.06, 0.00 to 0.84), but the certainty of evidence was low. 17OHPC (17α-hydroxyprogesterone caproate; 0.68, 0.43 to 1.02, moderate certainty), vaginal pessary (0.65, 0.39 to 1.08, moderate certainty), and fish oil or omega 3 (0.30, 0.06 to 1.23, moderate certainty) might also reduce preterm birth <34 weeks compared with placebo or no treatment. For the fetal outcome of perinatal death (30 trials, 12 119 pregnant women) and with placebo or no treatment as the comparator, vaginal progesterone was the only treatment that showed clear evidence of benefit for this outcome (0.66, 0.44 to 0.97, moderate certainty). 17OHPC (0.78, 0.50 to 1.21, moderate certainty), McDonald cerclage (0.59, 0.33 to 1.03, moderate certainty), and unspecified cerclage (0.77, 0.53 to 1.11, moderate certainty) might reduce perinatal death rates, but credible intervals could not exclude the possibility of harm. Only progesterone treatments are associated with reduction in neonatal respiratory distress syndrome, neonatal sepsis, necrotising enterocolitis, and admission to neonatal intensive care unit compared with controls. CONCLUSION: Vaginal progesterone should be considered the preventative treatment of choice for women with singleton pregnancy identified to be at risk of spontaneous preterm birth because of a history of spontaneous preterm birth or short cervical length. Future randomised controlled trials should use vaginal progesterone as a comparator to identify better treatments or combination treatments. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020169006.

Developing a topic-based repository of clinical trial individual patient data: experiences and lessons learned from a pilot project.

BACKGROUND: Building a dataset of individual participant data (IPD) for meta-analysis represents considerable research investment as well as collaboration across multiple institutions and researchers. Making arrangements to curate and share the dataset beyond the IPD meta-analysis project for which it was established, for reuse in future research projects, would maximise the value of this investment. METHODS: Our aim was to establish the Cochrane repository for individual patient data from clinical trials in pregnancy and childbirth (CRIB) as an example of how an IPD repository could become part of Cochrane infrastructure. We believed that establishing CRIB under Cochrane auspices would engender trust and encourage trial investigators to share data, and at the same time position Cochrane to take steps towards expanding the number of reviews with IPD synthesis. RESULTS: CRIB was designed as a web-based platform to receive, host and facilitate onward sharing of de-identified data. Development was not straightforward and we did not fully achieve our aim as intended. We describe the challenges encountered and suggest ways that future repositories might overcome these. In particular, securing the legal agreements required to facilitate data sharing proved to be the main barrier, being time-consuming and more complex than anticipated. CONCLUSIONS: We would recommend that researchers conducting IPD meta-analysis should consider discussing the option to transfer the curated IPD datasets to a repository at the end of the initial meta-analysis and this should be recognised within the data sharing agreements made with the original data contributors.

Which method is best for the induction of labour? A systematic review, network meta-analysis and cost-effectiveness analysis.

BACKGROUND: More than 150,000 pregnant women in England and Wales have their labour induced each year. Multiple pharmacological, mechanical and complementary methods are available to induce labour. OBJECTIVE: To assess the relative effectiveness, safety and cost-effectiveness of labour induction methods and, data permitting, effects in different clinical subgroups. METHODS: We carried out a systematic review using Cochrane methods. The Cochrane Pregnancy and Childbirth Group's Trials Register was searched (March 2014). This contains over 22,000 reports of controlled trials (published from 1923 onwards) retrieved from weekly searches of OVID MEDLINE (1966 to current); Cochrane Central Register of Controlled Trials (The Cochrane Library); EMBASE (1982 to current); Cumulative Index to Nursing and Allied Health Literature (1984 to current); ClinicalTrials.gov; the World Health Organization International Clinical Trials Registry Portal; and hand-searching of relevant conference proceedings and journals. We included randomised controlled trials examining interventions to induce labour compared with placebo, no treatment or other interventions in women eligible for third-trimester induction. We included outcomes relating to efficacy, safety and acceptability to women. In addition, for the economic analysis we searched the Database of Abstracts of Reviews of Effects, and Economic Evaluations Databases, NHS Economic Evaluation Database and the Health Technology Assessment database. We carried out a network meta-analysis (NMA) using all of the available evidence, both direct and indirect, to produce estimates of the relative effects of each treatment compared with others in a network. We developed a de novo decision tree model to estimate the cost-effectiveness of various methods. The costs included were the intervention and other hospital costs incurred (price year 2012-13). We reviewed the literature to identify preference-based utilities for the health-related outcomes in the model. We calculated incremental cost-effectiveness ratios, expected costs, utilities and net benefit. We represent uncertainty in the optimal intervention using cost-effectiveness acceptability curves. RESULTS: We identified 1190 studies; 611 were eligible for inclusion. The interventions most likely to achieve vaginal delivery (VD) within 24 hours were intravenous oxytocin with amniotomy [posterior rank 2; 95% credible intervals (CrIs) 1 to 9] and higher-dose (≥ 50 µg) vaginal misoprostol (rank 3; 95% CrI 1 to 6). Compared with placebo, several treatments reduced the odds of caesarean section, but we observed considerable uncertainty in treatment rankings. For uterine hyperstimulation, double-balloon catheter had the highest probability of being among the best three treatments, whereas vaginal misoprostol (≥ 50 µg) was most likely to increase the odds of excessive uterine activity. For other safety outcomes there were insufficient data or there was too much uncertainty to identify which treatments performed 'best'. Few studies collected information on women's views. Owing to incomplete reporting of the VD within 24 hours outcome, the cost-effectiveness analysis could compare only 20 interventions. The analysis suggested that most interventions have similar utility and differ mainly in cost. With a caveat of considerable uncertainty, titrated (low-dose) misoprostol solution and buccal/sublingual misoprostol had the highest likelihood of being cost-effective. LIMITATIONS: There was considerable uncertainty in findings and there were insufficient data for some planned subgroup analyses. CONCLUSIONS: Overall, misoprostol and oxytocin with amniotomy (for women with favourable cervix) is more successful than other agents in achieving VD within 24 hours. The ranking according to safety of different methods was less clear. The cost-effectiveness analysis suggested that titrated (low-dose) oral misoprostol solution resulted in the highest utility, whereas buccal/sublingual misoprostol had the lowest cost. There was a high degree of uncertainty as to the most cost-effective intervention. FUTURE WORK: Future trials should be powered to detect a method that is more cost-effective than misoprostol solution and report outcomes included in this NMA. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013005116. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Choosing important health outcomes for comparative effectiveness research: a systematic review.

BACKGROUND: A core outcome set (COS) is a standardised set of outcomes which should be measured and reported, as a minimum, in all effectiveness trials for a specific health area. This will allow results of studies to be compared, contrasted and combined as appropriate, as well as ensuring that all trials contribute usable information. The COMET (Core Outcome Measures for Effectiveness Trials) Initiative aims to support the development, reporting and adoption of COS. Central to this is a publically accessible online resource, populated with all available COS. The aim of the review we report here was to identify studies that sought to determine which outcomes or domains to measure in all clinical trials in a specific condition and to describe the methodological techniques used in these studies. METHODS: We developed a multi-faceted search strategy for electronic databases (MEDLINE, SCOPUS, and Cochrane Methodology Register). We included studies that sought to determine which outcomes/domains to measure in all clinical trials in a specific condition. RESULTS: A total of 250 reports relating to 198 studies were judged eligible for inclusion in the review. Studies covered various areas of health, most commonly cancer, rheumatology, neurology, heart and circulation, and dentistry and oral health. A variety of methods have been used to develop COS, including semi-structured discussion, unstructured group discussion, the Delphi Technique, Consensus Development Conference, surveys and Nominal Group Technique. The most common groups involved were clinical experts and non-clinical research experts. Thirty-one (16%) studies reported that the public had been involved in the process. The geographic locations of participants were predominantly North America (n = 164; 83%) and Europe (n = 150; 76%). CONCLUSIONS: This systematic review identified many health areas where a COS has been developed, but also highlights important gaps. It is a further step towards a comprehensive, up-to-date database of COS. In addition, it shows the need for methodological guidance, including how to engage key stakeholder groups, particularly members of the public.